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Background: Fatty acid binding protein-2 (FABP-2) is involved in the metabolism of lipids in the intestine. FABP-2 Ala54Thr polymorphism involves a transition of G to A at codon 54 of FABP-2, resulting in an amino acid substitution Ala54 to Thr54 and is associated with elevated fasting triglycerides in some hyperlipidemic populations. In current genome builds and gene databases the variant of the Ala54Thr FABP-2 (rs 1 799 883) is annotated as c.163A>G (p. Thr55Ala). Aim and Objective: The status of this polymorphism in hyperlipidemic Asian Indians from North India has not been investigated. This study was aimed to evaluate the distribution of the polymorphic variants of the Ala54Thr FABP-2 and their association with lipids in hyperlipidemic subjects. Methods: Ala54Thr FABP-2 polymorphism in both hyperlipidemic (n = 210) and normolipidemic (n = 342) subjects was assessed by PCR-RFLP. Results: Ala54Thr genotypes and alleles distribution did not differ between the hyperlipidemic and normolipidemic groups. The heterozygous genotype FABP-2 Ala/Thr was significantly associated with higher levels of triglycerides and very low-density lipoproteins as compared to the homozygous variant (Thr/Thr) genotype and the wild type homozygous (Ala/Ala) genotype. Conclusions: The heterozygous genotype FABP-2 Ala54Thr is a risk factor for the development of hypertriglyceridemia and increased levels of VLDL-c in Asian Indians from North India. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is a neurovascular disorder and is clinically characterized by episodic attacks of mild to severe headaches. Due to the involvement of multiple environmental and genetic factors, it has become a much more complex neurological condition to understand. Apart from the environmental variables, a plethora of genes have been implicated, and one such example is ESR1. The present study was focused to find out the association of two important polymorphisms, namely, PvuII and XbaI of the ESR1 with migraine in the population of Jammu and Kashmir (UT). Methods: The PCR-RFLP genotyping method was utilized to detect PvuII and XbaI polymorphism, and the result was confirmed by statistical analysis. Results: Although we did not find a signification association of ESR-PvuII polymorphism with migraine susceptibility {OR: 1.14 at 95% CI [0.76–1.71] (p value 0.5)}, a strong association was found with the clinical subtype of migraine; migraine with aura (MA) {OR: 2.014 at 95% CI [1.069–3.792] (p value 0.028)}. Furthermore, a significant association of ESR-XbaI polymorphism was observed with migraine {OR: 1.908 at 95% CI [1.252–2.907] (p value 0.002) and its both clinical subtypes; migraine without aura (MO) {OR: 1.870 at 95% CI [1.186–2.950] (p value 0.006)} and MA {OR: 2.014 at 95% CI [1.069–3.792] (p value 0.028)}. Conclusion: In conclusion, ESR1-XbaI polymorphism is significantly associated with migraine risk including both subtypes (MA and MO) in the North Indian population of Jammu. [ABSTRACT FROM AUTHOR]

The involvement of many putative genetic factors makes osteoporosis a complex disease. With increasing longevity of the Indian population, it's now being realized that, as within the West, osteoporotic fractures are also a significant explanation for morbidity and mortality in postmenopausal women. Studies have suggested that the genetic component liable for bone mass could be linked to single nucleotide polymorphisms. Therefore, this study is aimed to research the role of seven gene polymorphisms previously associated with bone phenotype in a cohort of postmenopausal South Indian women from Tamil Nadu. The subjects for the study (n = 300) included 100 osteoporotic women (age 59.3 ± 9.26), 100 osteopenic women (age 55.6 ± 8.17) and 100 non-osteoporotic women as controls (age 55.4 ± 8.85).Genetic polymorphisms were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Case–control genetic association analysis of BsmI of the VDR and BstBI of the PTH gene showed a significant allelic association with low bone mineral density amongst the osteoporotic postmenopausal women. The association of BMD with the VDR gene polymorphisms revealed that the average BMD in the BsmI polymorphism with the recessive genotype GG in osteoporotic women was significantly reduced compared with the average BMD in osteoporotic women with AA and AG genotypes. In the BstBI polymorphism, the BMD in the osteoporotic subjects were significantly lower in the AA group than in the GA and GG groups. These results provide evidence for an independent association between BMD and rs1544410 in VDR and rs6254 in PTH and may contribute in being a possible genetic marker for predicting the disease susceptibility in the population tested. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of end-stage renal disease in children. While certain nephrogenic genes have been incriminated in these malformations, data to identify the frequency of gene polymorphisms in Asian Indian children with CAKUT are scarce. This study was done to identify the effect of polymorphisms in paired-box gene 2 (PAX2), bone morphogenetic protein (BMP)-4, angiotensin-converting enzyme (ACE), and angiotensin II receptor Type 2 (AGTR2) nephrogenic genes on the development of CAKUT. Materials and Methods: In this prospective cohort study, 158 children <12 years old (86 cases with CAKUT and 72 age-matched controls) were analyzed. DNA from both sets was extracted from peripheral blood using the Keygen DNA extraction kit, and single-nucleotide gene polymorphisms (SNPs) in PAX2, BMP-4, ACE, and AGTR2 nephrogenic genes were detected by polymerase chain reaction (PCR) using previously published primers and PCR conditions. Results: The presence of A allele SNP for AGTR2 gene at rs3736556 was found to be significantly correlated with the development of ureteropelvic junction obstruction and vesicoureteral reflux (VUR) with the TT allelic genotype having a lower incidence of pelviureteric junction obstruction (odds ratio [OR] 0.18 [95% confidence interval [CI], 0.06–0.55], P = 0.01) and VUR (OR 0.31 [95% CI, 0.11–0.91], P = 0.03). Furthermore, on substratification of the patients with the presence of the A allele of AGTR2, 24 out of 27 patients with scarring were found to harbor the D allele of the ACE gene, thus predisposing them to further renal damage. Conclusion: This study points to early evidence in the implication of nephrogenic genes in development as well as predisposition to renal injury in Asian Indian patients with CAKUT. [ABSTRACT FROM AUTHOR]

• The first population data for X-STRs in Malaysian Indian. • Highly discriminative for complex kinship investigations. • Qiagen Investigator® Argus X-12 kit. X-chromosome short tandem repeats (X-STRs) are useful for human identification, especially in complex kinship scenarios. Since forensic statistical parameters vary among populations and the X-STRs population data for the diverse population of Peninsular Malaysia's are unavailable, this attempt for Indians (n = 201) appears forensically relevant to support the 12 X-STRs markers' evidential value for human identification in Malaysia. The Qiagen Investigator® Argus X-12 QS kit showed that DXS10135 was the most polymorphic locus with high genetic diversity, polymorphism information richness, heterozygosity, and exclusion power. Based on allele frequencies, the strength of discrimination and mean exclusion chance (MEC Krüger , MEC Kishida , MEC Desmarais , and MEC DesmaraisDuo) values for the Malaysian Indians were ≥0.999997790686228. As for haplotype frequencies, the overall discrimination power and mean exclusion probability (MEC Krüger , MEC Kishida , MEC Desmarais , and MEC DesmaraisDuo) were ≥0.9999984801951. The genetic distance, neighbor-joining phylogenetic tree, and principal component analysis also supported the evidential value of the 12 X-STRs markers for forensic practical caseworks in Malaysia. [ABSTRACT FROM AUTHOR]

There is growing interest in understanding the genetic mechanisms underlying dyslexia. Accordingly, the literature on dyslexia is replete with shreds of evidence linking genes and their genetic markers with dyslexia among different populations. Even though genetic inquiries into dyslexia in the Asian population has gained interest in recent years, very little is known about the genes and their polymorphisms associated with dyslexia in the Indian population. To this end, we provide a systematic literature review that yields a dossier of genetic research that manifests the effect of the genes and their polymorphisms associated with dyslexia susceptibility in the Indian population. We conclude that the polymorphisms of the DYX1C1 and KIAA0319 genes deserve attention in replication studies on the Indian population in order to gain insight into the genetic etiology of dyslexia. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy is known to be a leading complication of diabetes mellitus, characterized by diverse aspects such as high urinary albumin level, elevated blood pressure, and genetic susceptibility leading to end-stage renal disease. The current study was carried out to investigate the association of eNOS and TGFβ1 gene polymorphisms in the progression of diabetic nephropathy among type 2 diabetic patients in the South Indian population. The eNOS and TGFβ1 genetic variants were genotyped in 280 T2DM patients, 140 with DN, 140 without DN, and 140 controls. Genotyping was performed using ARMS PCR and the genomic variants were confirmed by the Sanger sequencing method. Results: A significant (p < 0.05) association was observed in the genotypic frequencies of eNOS (G > T) polymorphism in the T2DM patients with diabetic nephropathy when compared to controls. The frequency of TT (heterozygous) genotype was observed to increase in patients with type 2 diabetes and DN when compared to the diabetic patients without DN and controls. This indicates that diabetic patients with TT genotype are at an increased risk to develop DN. However, TGFβ1 (G > C) polymorphism did not show any association in the allele and genotypic frequencies with DN when compared with T2DM and controls. Conclusion: The results of the study propose a strong influence of TT genotype of eNOS gene be significantly linked with diabetic nephropathy in T2DM patients. Whereas no association was examined concerning TGFβ1 gene polymorphism and DN. Nevertheless, large sample size studies are required to confirm the part of these genetic variants in the development of DN. [ABSTRACT FROM AUTHOR]

Aim and objective: The aim of the study was to investigate the relationships between insulin receptor substrate (IRS) 1 (Gly972Arg) and IRS2 (Gly1057Asp) genes with obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in Asian Indians. Method: A total of 410 overweight/obese subjects (130 with OSA with NAFLD, 100 with OSA without NAFLD, 95 without OSA and with NAFLD and 85 without OSA and without NAFLD) were recruited. Degree of NAFLD was based on liver ultrasound and of OSA on overnight polysomnography. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by gene sequencing. Result: Mean values of blood pressure, body fat markers, blood glucose, lipids, liver function, and markers of insulin resistance were significantly increased in OSA and NAFLD subjects (p<0.05). In addition, according to age (years) categories, blood pressure, blood glucose, lipids, obesity markers, and markers of insulin resistance were significantly higher in 45–60 years group as compared to 20–45 years group (p<0.05). In IRS1 gene, the genotype frequency (%) of Arg/Arg was significantly higher in NAFLD and OSA subjects. In addition, Gly/Arg genotype of IRS1 gene was associated with significantly higher body mass index, fat mass, %body fat, triglycerides, cholesterol, alkaline phosphate, aspartate transaminase, fasting insulin and HOMA-IR levels in OSA and NAFLD subjects. No significant difference in genotype frequencies of IRS2 was observed between four groups. Further we found that subjects carrying IRS1 Gly/Arg (OR 4.49, 95% C.I. 1.06–12.52, p = 0.002) genotype possess a much higher risk of OSA and NAFLD compared to IRS2 Gly/Asp (OR 1.01, 95% C.I. 0.8–2.56, p = 0.05). In sub group analysis of IRS1 Gly/Arg have significant differences between the mild, moderate and severe group (P<0.05). In addition, patients with the 'Gly' allele were inclined to develop more severe OSA. Conclusion: We concluded that Asian Indian subject carrying the allele Gly972Arg polymorphism of IRS1 is predisposed to develop OSA and NAFLD. [ABSTRACT FROM AUTHOR]

Background: Plasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. In this study, we aim to examine the association of omentin gene polymorphism with serum adiponectin levels and cardiometabolic health status using a genetic approach, and investigate whether these associations are modified by lifestyle factors. Methods: The study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The omentin A326T (rs2274907) single nucleotide polymorphism (SNP) was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Results: The 'A' allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p = 1.90 x 10−47). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p = 7.47x10-10). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of 'A' allele with cardiometabolic health status disappeared (p = 0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons). Conclusions: Our findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in Asian Indians. Before strategies to promote adiponectin modulation could be implemented, further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Introduction: Women with family history of diabetes (FHD) are at significantly increased risk of developing gestational diabetes mellitus which may eventually lead to type 2 diabetes mellitus (T2DM) in later life. Objective: This study investigates the role of FHD on metabolic markers and gene polymorphisms and hence on T2DM susceptibility in nondiabetic pregnant women and the subsequent risks in their newborns. Materials and Methods: The present study was conducted on 200 healthy (nondiabetic and normotensive) adult Asian Indian women, including 100 with and 100 without FHD, living in and around Kolkata, India. During the gestational period, they were studied twice and followed up till delivery. During delivery, both mothers' venous blood and cord blood were collected to estimate serum CRP, glucose, and lipid profiles of the respective mothers and their newborns. Genotyping of PPARγ and TCF7L2 polymorphisms was done from these blood samples. Results: A comparison of the metabolic variables among the subjects with and without FHD revealed significant differences among them. We also found close relationship between mothers and their newborn babies in terms of both PPARγ (rs1801282) C/G and TCF7L2 (rs7903146) C/T polymorphisms. More specifically, genotyping results for mothers with FHD and their newborn babies showed high concordance in inheritance of alleles: (i) for PPARγ via the risk allele G (74.0%) which is carried over to the newborn babies (64.5%) and (ii) for TCF7L2 via the risk allele T (73.0%) which is carried over to the newborn babies (68.5%). Conclusion: This study leads to the conclusion that Asian Indian women population based in Kolkata, India, are ethnically and genetically predisposed to the risk factors of diabetes through FHD, which is reflected in their gestational phase, and it has a significant implication on their birth outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Women with family history of diabetes (FHD) are at significantly increased risk of developing gestational diabetes mellitus which may eventually lead to type 2 diabetes mellitus (T2DM) in later life. Objective: This study investigates the role of FHD on metabolic markers and gene polymorphisms and hence on T2DM susceptibility in nondiabetic pregnant women and the subsequent risks in their newborns. Materials and Methods: The present study was conducted on 200 healthy (nondiabetic and normotensive) adult Asian Indian women, including 100 with and 100 without FHD, living in and around Kolkata, India. During the gestational period, they were studied twice and followed up till delivery. During delivery, both mothers' venous blood and cord blood were collected to estimate serum CRP, glucose, and lipid profiles of the respective mothers and their newborns. Genotyping of PPARγ and TCF7L2 polymorphisms was done from these blood samples. Results: A comparison of the metabolic variables among the subjects with and without FHD revealed significant differences among them. We also found close relationship between mothers and their newborn babies in terms of both PPARγ (rs1801282) C/G and TCF7L2 (rs7903146) C/T polymorphisms. More specifically, genotyping results for mothers with FHD and their newborn babies showed high concordance in inheritance of alleles: (i) for PPARγ via the risk allele G (74.0%) which is carried over to the newborn babies (64.5%) and (ii) for TCF7L2 via the risk allele T (73.0%) which is carried over to the newborn babies (68.5%). Conclusion: This study leads to the conclusion that Asian Indian women population based in Kolkata, India, are ethnically and genetically predisposed to the risk factors of diabetes through FHD, which is reflected in their gestational phase, and it has a significant implication on their birth outcomes. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a multifaceted illness affecting ~ 0.3% of the world population. The genetic complexity of PD has not been, fully elucidated. Several studies suggest that mitochondrial DNA variants are associated with PD.Objective: Here, we have explored the possibility of genetic association between mitochondrial haplogroups as well as three independent SNPs with PD in a representative east Indian population.Methods and Material: The Asian mtDNA haplogroups: M, N, R, B, D, M7, and 3 other SNPs: 4336 T/C, 9055 G/A, 13708 G/A were genotyped in 100 sporadic PD patients and 100 matched controls via conventional PCR-RFLP-sequencing approach.Results: The distribution of mtDNA haplogroups, as well as 3 single polymorphisms, did not show any significant differences (P > 0.05) between patients and controls.Conclusion: This is the first of its kind of study from India that suggests no association of selected mitochondrial DNA variations with PD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the frequency and the association of Thrombospondin 1 (THBS1) gene single nucleotide polymorphisms (SNPs) in Asian Indian patients with optical full thickness corneal grafting surgery.Methods: Prospective case-control analysis of optical penetrating keratoplasty patients with and without immune rejection and controls for genotyping of 3 THBS1 gene SNPs (rs1478604 A>G; rs2228261 C>T; rs2228262 A>G) by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS PCR).Results: Among 58 patients [45 with immune allograft rejection (DNA isolation was possible in 38 samples) and 13 without immune corneal allograft rejection] and 65 controls, allele frequencies observed for rs1478604 (A>G) are A: 69.7% and 72.6%, G: 30.2% and 27.3%; for rs2228261 (C>T) are T: 70.2% and 62.3%, C: 29.7% and 37.6%; and for rs2228262 (A>G) A: 97.4% and 98.4%; G 2.5% and 1.5% respectively. Genotype frequencies were rs1478604 (A>G) AA: 57.8% and 59.3%, AG 23.6% and 26.5%; GG 18.4% and 14%; for rs2228261 (C>T) TT: 40.5% and 33.8%, TC: 59% and 56.9%, CC: 0% and 9.2%; for rs2228262 (A>G) AA: 94.8% and 96.8%, AG: 5.1% and 3.1% in rejection and controls respectively. The allele and genotype frequency for the 3 described THSB1 SNPs did not show any difference between the corneal graft immune rejection patients and controls.Conclusion: Asian Indian population evaluated for THBS1 gene SNPs by ARMS PCR genotyping in Asian Indian population did not show any genetic association to immune rejection occurrence in our study. [ABSTRACT FROM AUTHOR]

CAD (Coronary Artery Disease) morbidity is becoming an endemic worldwide. Recently, the role of pro- and anti-inflammatory cytokines in the development of atherosclerotic plaques has been explored, but the association of their genetic polymorphisms and CAD has yet not been established. The present study aimed to investigate the association of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) polymorphisms and the risk of CAD in North Indian population. 1000 subjects (500 angiographically confirmed CAD patients and 500 controls) were genotyped by ARMS-PCR. Results revealed a significant risk association of both the polymorphisms with CAD. The heterozygous and the mutant genotypes of IL-8 rs4073 were both found to be associated with the risk of disease after adjusting for the confounders (padj < 0.001, ORadj 3.121, 95% CI 1.926-5.056 and padj < 0.001, ORadj 3.116, 95% CI 1.952-4.973, respectively), but only the mutant AA genotype of IL-10 rs1800872 correlated with risk of disease with padj < 0.001, ORadj 4.106, 95% CI 2.160-7.806). Stratifying the samples on the basis of gender revealed CAD in heterozygous and mutant in males (padj < 0.001, ORadj 3.693, 95% CI 2.031-6.716; padj < 0.001, ORadj 3.288, 95% CI 1.848-5.851, respectively) and only the mutant to be associated with risk of disease in females (padj = 0.010, ORadj 2.867, 95% CI 1.284-6.404) for IL-8 rs4073, whereas only the mutant genotype AA of IL-10 rs1800872 associated with CAD risk in males (padj < 0.001, ORadj 5.821, 95% CI 2.831-11.970). Stratified analysis based on age showed a significant higher risk in the heterozygous and mutant genotype in subjects below 40 years of age (padj = 0.039, ORadj 5.052, 95% CI 1.081-23.602; and padj = 0.025, ORadj 5.533, 95% CI 1.239-24.704, respectively) compared with the heterozygous and mutant genotype association of the risk of disease in subjects above 40 years of age (padj < 0.000, ORadj 2.964, 95% CI 1.747-5.027; and padj < 0.000, ORadj 2.859, 95% CI 1.716-4.762, respectively) in IL-8 rs4073. For IL-10 rs1800872, risk association was seen only in subjects above 40 years of age (padj < 0.001, ORadj 5.049, and 95% CI 2.414-10.561). The present study exhibited associations of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) with CAD in the North Indian population and also that the associations are gender and age dependent. [ABSTRACT FROM AUTHOR]

Background & objectives: Asian Indians have been shown to have a high prevalence of metabolic syndrome (MetS), related to insulin resistance and possibly genetic factors. The aim of this study was to determine the genetic patterns associated with MetS in Asian Indians living in Durban, South Africa. Methods: Nine hundred and ninety nine participants from the Phoenix Lifestyle Project underwent clinical, biochemical and genetic assessment. MetS was diagnosed according to the harmonized definition. The apolipoprotein A5 Q139X, lipoprotein lipase (LPL) Hinf I, human paraoxonase 1 (PON1) 192Arg/Gln, cholesteryl ester transfer protein (CETP) Taq1B, adiponectin 45T>G and leptin (LEP) 25CAG were genotyped by real-time polymerase chain reaction in participants with and without MetS. Univariate-unadjusted and multivariate-adjusted relations were conducted for all analyses. Results: The prevalence of MetS was high (49.0%). More females had MetS than males (51.0 vs 42.8%). There was no significant difference in the distribution of genotypes between participants with MetS and those without. Males with the MetS who had the adiponectin TG genotype and human paraoxonase 1 AA genotype were more likely to have reduced high-density lipoprotein cholesterol (HDL-C) (P=0.001) and higher systolic blood pressure (P=0.018), respectively. Interpretation & conclusions: About half of the Asian Indians living in Phoenix had MetS. No association between the polymorphisms studied and the risk for MetS was observed. The adiponectin TG genotype may be associated with reduced HDL-C and the human paraoxonase 1 AA genotype with hypertension in males. This suggested that lifestyle factors were the major determinant for MetS in this ethnic group and the genetic risk might be related to its component risk factors than to MetS as an entity. [ABSTRACT FROM AUTHOR]

Background and aim Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. Methods Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. Results The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P < 0.005) and 2.24 (P < 0.005) respectively. SNP 192 Q > R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. Conclusion PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population. [ABSTRACT FROM AUTHOR]

Background Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α − 308 (G/A), TNF-β + 252 (A/G), IL-6 − 174 (G/C) and IL-6 − 597 (G/A), and IFN-ɣ + 874 (T/A) with coronary artery disease (CAD) among north Indian patients. Materials and methods 143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-α − 308 (G/A) (rs1800797), TNF-β + 252 (A/G) (rs909253), IL-6 − 174 (G/C) (rs1800795), IL6 − 597 (G/A) (rs1800797), and IFN-ɣ + 874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p ≤ 0.05 was considered significant. Results Significant risk association with CAD was found for TNF-α − 308 (G/A) “A” allele (OR = 5.6, CI 1.8–17.4, p = 0.001) and TNF-β + 252 (A/G) “G” allele (OR = 3.4, CI = 1.9–6.0, p < 0.001). However, no statistical significance was found for IL-6 − 174 (G/C) or IL6 − 597 (G/A), with CAD. TNF-α − 308 (G/A), and TNF-β + 252 (A/G) haplotype “GG” “AG” increased CAD risk significantly (GG haplotype, adjusted OR = 2.6, CI 1.4–5.0, p = 0.003 and AG haplotype OR = 8.5, CI 2.2–33.35, p = 0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet. Discussion The present study found significant risk association for TNF-α − 308 (G/A), and TNF-β + 252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population. [ABSTRACT FROM AUTHOR]

• Low vitamin D levels are found to be associated with increased risk of postpartum depression. • The study explored the association between VDBP variants rs7041 and rs4588 and PPD risk. • The VDBP variants rs7041 and rs4588 and their haplotypes are not significantly associated with PPD susceptibility in our South Indian population. • However, the risk genotypes of VDBP SNPs rs4588 and rs7041 were associated with lower circulating serum vitamin D levels that might lead to PPD susceptibility. Low vitamin D levels have been implicated in postpartum depressive disorders (PPD). Our study aimed to demonstrate the association of Vitamin D Binding Protein (VDBP) genetic variants rs7041 and rs4588 with susceptibility to PPD and to investigate their possible relationship with serum vitamin D and VDBP levels in Indian women with PPD. A cross-sectional study involved 330 cases and 330 controls. Depressive symptoms were assessed using Edinburg Postnatal Depression Scale. Genotyping of SNPs was done by Taqman 5'allelic discrimination assay. Estimation of serum 25 hydroxyvitamin D [25(OH) D] and VDBP levels were done by ELISA. Serum total, free and bioavailable 25(OH) D levels were significantly lower in cases compared to controls, with similar levels of VDBP between the two groups. The study results showed that the VDBP rs4588 variant genotype AA was significantly associated with lower circulating levels of total 25(OH) D in cases. Also, the VDBP rs7041 variant TT genotype demonstrated significantly lower levels of total, free and bioavailable 25(OH) D levels in controls. However, VDBP rs7041 and rs4588 variants were not associated with PPD susceptibility. Also, VDBP haplotypes showed no association with PPD susceptibility. Our results demonstrated that VDBP polymorphisms rs4588 and rs7041 and their haplotypes are not associated with PPD susceptibility in the South Indian population. However, vitamin D levels were found to be influenced by the risk genotypes of VDBP SNPs rs4588 and rs7041. [ABSTRACT FROM AUTHOR]

Dengue infection is caused by flavivirus is one of the leading cause of mortality. There are certain factors which play role in the transformation of a mild form of the disease (DF) into a severe form (DHF) but the most important ones are: viral strain virulence, host genetics, and host immune status. In severe dengue infection, plasma leakage occurs due to vascular endothelial cell activation through expression of adhesion molecule like intercellular cell adhesion molecule-1 (ICAM-1). A total of 100 dengue patients (DF; n = 53 and DHF/DSS; n = 47) and 200 healthy controls were included in the study. ICAM-1 K469E genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). Expression of ICAM-1 mRNA was done by Real time reverse transcription- PCR (rRT-PCR). Patients with homozygous genotype (EE) have 3.22 fold risk (P = 0.008) of developing severe form of disease (DHF/DSS) as compared to other genotypes. Patients with DHF/DSS exhibit higher expression of ICAM-1 mRNA as compared to dengue fever and controls (P = 0.001 and < 0.001). Patients (DHF/DSS) with homozygous (EE) genotype exhibit higher expression of ICAM-1 mRNA when compared with wild type (KK) genotype (P = 0.005). This study suggests a possible association between the ICAM-1 polymorphism and the disease severity. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE) is the key enzyme of the renin angiotensin system (RAS) which maintains the blood pressure homeostasis in our body. The association of the ACE insertion/deletion (I/D) polymorphism with essential hypertension has been demonstrated by many studies. The purpose of the present study is to investigate the association of the insertion/deletion polymorphism of the ACE gene with hypertension and additive diseases in North Indian population. In total, 222 hypertensive and 218 normotensive adults participated in this hospital-based study. Anthropometric measures, lipids profiles, blood glucose, and blood pressure (BP) measures were collected from participants. ACE I/D polymorphism was determined by using insertion-specific amplification. The mean ages of study groups were 50.35 ± 12.40 and 47.32 ± 11.94 for cases and controls, respectively. Significant differences were observed in the frequencies of DD, ID, and II genotypes among the hypertensive and normotensive groups which were found to be 29.7%, 38.7%, and 31.5% vs. 53.7%, 23.4%, and 22.9%, respectively. It has been observed that the ACE ID genotype was significantly (p< 0.05) higher in hypertensive subjects, whereas, the DD genotype was significantly (p< 0.05) higher in control subjects. A strong association was found between cardiovascular diseases (CVDs) and ID genotype [p= 0.017, odds ratio (OR) = 3.091, 95% confidence interval (CI) = 1.224–7.807]. ID [p= 0.002, OR = 2.020, 95% CI = 1.281–3.185] and II [p= 0.032, OR = 1.677, 95% CI = 1.044–2.694] genotypes are more prone to diabetes with hypertension. This finding suggests that ACE insertion/deletion polymorphism is associated with hypertension and additive diseases in North Indians. [ABSTRACT FROM AUTHOR]

Genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with unconjugated hyperbilirubinemia. The present study was undertaken to validate the association of SNPs with development of hyperbilirubinemia in Indian neonates. Genotyping of five SNPs in two candidate genes was performed in 126 infants with hyperbilirubinemia and 181 controls by PCR-RFLP, Gene Scan analysis and direct DNA sequencing. Genetic polymorphisms of the UGT1A1 promoter, specifically the -3279 T➔G phenobarbital responsive enhancer module (rs4124874) and (TA)7 dinucleotide repeat (rs8175347) as well as the coding region variants (rs2306283 and rs4149056) of the OATP2 gene were significantly higher among the cases than the controls. The presence of the mutant haplotypes either in homozygous, heterozygous or compound heterozygous state had a significant effect on neonatal hyperbilirubinemia as well as on the requirement of phototherapy than those with the wild haplotype. Further, a significantly higher number of hyperbilirubinemic cases had ≥3 variants than the controls (73.80% vs 40.36%, p<0.0001) and the mean total serum bilirubin levels and requirement of phototherapy also increased according to the number of variants co-expressed. This study demonstrates that UGT1A1 and OATP2 polymorphisms were associated with altered bilirubin metabolism and could be genetic risk factors for neonatal hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Abstract: Developmental Dyslexia (DD) is a heritable, complex genetic disorder characterized by specific impairment in reading and writing ability that is substantially below the expected reading ability given the person's chronological age, measured intelligence and age-appropriate education. More than ten susceptible genes have been identified for DD. A Single Nucleotide Polymorphism (SNP) of these genes was found to be associated with various phenotypes of DD. To identify the role of SNPs of four candidate genes namely, MRPL19/C2ORF3, ROBO1 and THEM2 in an Indian population, we genotyped eight SNPs of these genes in 157 children with DD and 212 normal readers using a MassARRAY technique with a MALDI-TOF MS analyzer. Power analysis of some of these SNPs showed >80% of power. Chi-square test, Odds Ratios (ORs), 95% Confidence Intervals (CIs) and Bonferroni's correction were applied to identify the significance of the genotyped SNPs and haplotypes. Our study failed to show any association of SNPs and haplotypes of these genes with DD in an Indian population. [Copyright &y& Elsevier]

Highlights: [•] First attempt from north India to dissect IL-17 axis in human tuberculosis (TB). [•] No association of IL17A and IL17F gene variants in pulmonary and extra-pulmonary TB [•] Correlated the serum cytokine levels and genotypes [•] IL17 variants might not be a major influencing gene for tuberculosis in north Indians. [ABSTRACT FROM AUTHOR]

Highlights: [•] Concomitant lead exposure and anemia remains high among children in India. [•] Lead exposure and low hemoglobin levels are associated with deficits in IQ. [•] Iron and lead share several toxicokinetic and toxicodynamic pathways. [•] Children with TF C2 variant allele may be more susceptible to neurotoxic effects of lead and less protected by hemoglobin. [ABSTRACT FROM AUTHOR]

(1) Background: Lysyl oxidase (LOX) plays a dual role in carcinogenesis and studies show a higher risk of cancer in LOX G473A variants. The present study evaluated the pattern of LOX G473A polymorphism (rs1800449) and serum LOX levels in ovarian cancer patients. (2) Methods: Serum LOX levels were estimated by enzyme linked immunosorbent assay (ELISA). A polymorphism of rs1800449 of LOX gene was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Selected samples were sequenced for external validation. (3) Results: A majority of study participants were from low socio-economic status. Serum LOX level was significantly higher in ovarian cancer patients as compared to control. Serum LOX level in early-stage ovarian cancer was significantly lower as compared to advanced stage (FIGO stage III & IV). Wild type GG genotype was used as reference. Genotypes AA were associated with a significant risk of epithelial ovarian cancer (OR 3.208; p value- 0.033). A allele of rs1800449 polymorphism of LOX gene, the odds ratio was 1.866 (95% Confidence Interval 1.112–3.16) p value = 0.017 (4) Conclusions: A allele of rs1800449 polymorphism of LOX gene presents an increased risk of ovarian cancer in East Indian population. Serum LOX levels could be a potential biomarker for the diagnosis and prognosis of ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate the association of functional single nucleotide polymorphisms (SNPs) of the endothelial nitric oxide synthase gene (eNOS) gene (T-786C, G894T) and one variable number tandem repeat polymorphism (aa 27VNTR bb) with reno-protective response to angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) therapy in North Indian type 2 diabetic mellitus (T2DM) subjects with cases having diabetic nephropathy (DN) and controls without DN. Method: We genotyped three polymorphisms of eNOS (two SNPs: T-786C, G894T and one 27 VNTR) in T2DM patients with overt nephropathy (cases: n =320) and T2DM patients without overt nephropathy (controls: n =490), using validated PCR-RFLP assays. These 810 North Indian T2DM patients treated with ACEI or ARB after diagnosis were followed up for 3 years. Percent changes in eGFR, urinary albumin excretion (UAE), serum creatinine at the end of 3 years of treatment were taken as end points of renoprotective response. Result: We observed that in normoalbuminuric patients, eNOS -786 CC genotype and haplotypes C-b-G and C-b-T were associated with lesser renoprotective response to ACEI. While, in macroalbuminurics, eNOS -786 CC genotype, haplotypes C-b-G and C-b-T and 27VNTR aa were associated with better renoprotective response to ACEI/ARB. Conclusion: Our results showed that eNOS T-786C CC genotype and 27VNTR individually and in interaction with other eNOS SNPs modulate renoprotective efficacy of ACEI and ARB in T2DM patients, depending on the status of proteinuria. [Copyright &y& Elsevier]

Abstract: Chewing betel quid may release chemical carcinogens including xenobiotics resulting in oral malignancy cases preceded by potential malignant lesions and conditions — Oral Submucous Fibrosis (OSF) being one of them. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes the nitrosamines and tannins. The present study investigated the association of polymorphisms at CYP1A1m1 (T3801C), m2 (A2455G), and CYP2E1 PstI site (nucleotide 21259) with the risk of OSF. The study was conducted on 75 OSF patients and 150 controls from an eastern Indian population. The above polymorphisms were analyzed by PCR-RFLP method. Analyses of data show that polymorphisms in CYP1A1m2 [OR=8.25 (4.31–15.80)]; CYP1A1m1 [OR=2.88 (1.57–5.24)] and CYP2E1 PstI site [OR=3.16 (1.10–9.04)] revealed significant association with OSF. Our results suggest that polymorphism in CYP1A1 and CYP2E1 may confer an increased risk for Oral Submucous Fibrosis. [Copyright &y& Elsevier]

Leukotrienes are potent inflammatory and lipid mediators that participate in atherosclerosis. We analyzed the association of Leukotriene gene (ALOX5, ALOX5AP, LTA4H, and LTC4S) polymorphisms and plasma Leukotriene B4 (LTB4) levels with coronary artery disease (CAD) in a representative cohort of Asian Indians. In all, 136 functional single nucleotide polymorphisms (SNPs) were selected using in silico tools. Forty-five polymorphic SNPs were ranked for predicted functional effect using FastSNP. Finally, 14 functional SNPs along with 10 SNPs identified from the literature were genotyped in 340 CAD patients and 340 controls. Plasma LTB4 levels were measured in 150 cases and 150 controls. None of the 24 SNPs showed significant association with CAD. Plasma LTB4 levels were higher in cases than in controls (76.42 ± 4.46pg/mL versus 60.89 ± 2.61 pg/mL) (P = 0.003), with greater risk being associated with the top quartile as compared to the bottom quartile after adjusting for potential confounders (OR 8.94, 95% CI 2.56-31.95; P = 0.001). Four SNPs in the LTA4H gene showed significant association with LTB4 levels (P < 0.05)of which rs1978331 (P = 0.035) remained significant after correction for multiple testing. LTB4 showed strong correlation with lipids (r = 0.24-34) only in cases. Our pilot study suggests that the association between Leukotrienes gene polymorphisms and CAD risk may be modulated through plasma LTB4 levels. [ABSTRACT FROM AUTHOR]

Abstract: Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Osteopontin (OPN) has been suggested to be associated with renal diseases characterized by tubulointerstitial fibrosis and proteinuria. However, information on association of genetic polymorphisms in OPN with diabetic nephropathy is lacking. Thus, the present study was designed with the aim to examine the association of an OPN gene promoter polymorphism with diabetic nephropathy in Asian Indians. OPN C-443T (rs11730582) polymorphism was determined in 1115 type 2 diabetic patients belonging to two independently ascertained cohorts using Real time PCR based Taqman assay. We observed a nearly threefold elevated risk of diabetic nephropathy among carriers of T allele and TT genotype of OPN C‐443T polymorphism. Further, this allele was found to be significantly associated with proteinuria and lower eGFR, a hallmark of diabetic nephropathy, in both our cohorts. This is the first study which suggests that OPN C-443T polymorphism may be a significant risk factor for diabetic nephropathy in type 2 diabetic patients. [Copyright &y& Elsevier]

Approximately, 4-11 % of the patients with idiopathic venous thrombosis (VT) show protein C (PC) deficiency. The molecular pathology of PC deficiency was analyzed in 102 patients; 98 healthy controls were also studied to assess the association of various polymorphisms with reduced PC levels. PROC gene mutations were detected only in 8 (7.8 %) patients with reduced PC levels. PROC promoter region CG polymorphisms showed statistically significant association with reduced PC levels ( p < 0.001). PC deficiency in Indian VT patients can, thus, largely be explained by PROC gene promoter CG polymorphisms; only a small fraction of the patients show specific mutations in PROC gene. [ABSTRACT FROM AUTHOR]

Background: To determine the association of the A55T and K153R polymorphisms of the Myostatin gene with obesity, abdominal obesity and lean body mass (LBM) in Asian Indians in north India. Materials and Methods: A total of 335 subjects (238 men and 97 women) were assessed for anthropometry, % body fat (BF), LBM and biochemical parameters. Associations of Myostatin gene polymorphisms were evaluated with anthropometric, body composition and biochemical parameters. In A55T polymorphism, BMI (p = 0.04), suprailiac skinfold (p = 0.05), total skinfold (p = 0.008), %BF (p = 0.002) and total fat mass (p = 0.003) were highest and % LBM (p = 0.03) and total LBM (Kg) were lowest (p = 0.04) in subjects with Thr/Thr genotype as compared to other genotypes. Association analysis of K153R polymorphism showed that subjects with R/R genotype had significantly higher BMI (p = 0.05), waist circumference (p = 0.04), %BF (p = 0.04) and total fat mass (p = 0.03), and lower %LBM (p = 0.02) and total LBM [(Kg), (p = 0.04)] as compared to other genotypes. Using a multivariate logistic regression model after adjusting for age and sex, subjects with Thr/Thr genotype of A55T showed high risk for high %BF (OR, 3.92, 95% Cl: 2.61-12.41), truncal subcutaneous adiposity (OR, 2.9, 95% Cl: 1.57-6.60)] and low LBM (OR, 0.64, 95% CI: 0.33-0.89) whereas R/R genotype of K153R showed high risk of obesity (BMI; OR, 3.2, 95% CI: 1.2-12.9; %BF, OR, 3.6, 95% CI: 1.04- 12.4), abdominal obesity (OR, 2.12, 95% CI: 2.71-14.23) and low LBM (OR, 0.61, 95% CI: 0.29-0.79). Conclusions/Significance:We report that variants of Myostatin gene predispose to obesity, abdominal obesity and low lean body mass in Asian Indians in north India. [ABSTRACT FROM AUTHOR]

Summary: Transforming growth factor (TGF)-β1, the most abundant isoform of TGF-β have been implicated in various stages of carcinogenesis such as epithelial to mesenchymal transition, enhanced expression of metalloproteases, down-regulation of cellular adhesion molecule, increased tumor motility and angiogenesis as well as local and systemic immunosuppression leading to a more aggressive and metastatic behavior. We assessed the association of TGF-β1 functional genetic polymorphisms at codon 10 (869 T>C) and 25 (915 G>C) of exon 1 in 140 patients with tobacco-related oral squamous cell carcinoma (OSCC) and 120 normal subjects by PCR–RFLP. The frequency of 869 CC genotype and C allele were significantly higher in patients as compared to controls (Pc , 0.024 and 0.0004, respectively) while no significant difference was observed in the frequency of 915 CC genotype and C allele. In logistic regression analysis CC genotype (OR, 3.87; 95% CI, 1.78–8.41) and C allele (OR, 2.20; 95% CI 1.51–3.20) appeared as susceptible while TT genotype and T allele as protective. In addition C869–C915 haplotype with OR of 2.48 at 95% CI, 1.51–4.06 significantly (P =0.0003) increased the risk of tobacco-related OSCC in Asian Indians. [Copyright &y& Elsevier]

Psoriasis is a common, chronic, recurrent, inflammatory, hyper proliferative disorder of the skin, which has a relatively high prevalence in the general population (0.6-4.8%). Linkage and association analyses in various populations have revealed a major locus for psoriasis susceptibility, PSORS1, at 6p21.3. Association of the disease with human leukocyte antigen (HLA) Cw6, corneodesmosin (CDSN) and the coiled-coil alpha-helical rod protein-1 (CCHCR1) has also been reported. Though the PSORS1 locus accounts for 30-50% of familial psoriasis in various global population groups, yet no studies have been published from the North Indian population. Some of the SNPs in HLA-C and CCHCR1 genes have been reported as markers for disease susceptibility. Therefore in the present study, DNA samples from psoriasis patients from North India were genotyped for polymorphisms in CCHCR1 and HLA-C genes. The allele frequencies were calculated for patients and controls, and were compared for odds ratio and confidence interval values. SNPn.7*22222 (rs12208888), SNPn.7*22333 (rs12216025), SNPn.9*24118 (rs10456057), CCHCR1_386 (rs130065), CCHCR1_404 (rs130076) and CCHCR1_1364 (rs130071) were found to be significant in psoriasis patients. Linkage disequilibrium analysis revealed two haplotypes (rs12208888, rs2844608, rs12216025, rs10456057, rs130065, rs130066, rs130068, rs130269, and rs12208888, rs2844608, rs12216025, rs130076, rs130066, rs130068, rs130269, rs130071) as highly susceptible haplotypes for psoriasis in the cohort studied. Preliminary analysis of the data also suggests the possibilities of ethnic group specific disease related polymorphisms, pending validation in future studies. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most prevalent disease in India according to the national survey conducted by NFHS 2 in 1998-399. Prostaglandin D2 (PGD2) is a bronchoconstriction inducing metabolite of arachidonic acid in the mast cells, which is produced on exposure to allergens and acts as a ligand for the Prostaglandin D2 Receptor (PTGDR). Polymorphisms in the PTGDR gene have been suggested to be involved in the mechanism of asthma. Objective: This is the first study conducted in India, investigating the role of PTGDR -441C/T} promoter polymorphism in asthma pathogenesis. Methods: A case-control study was performed with a total of 992 subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The PTGDR -441C/T polymorphism was genotyped by Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR). Results: Statistical analysis of the results between asthma cases and controls for the PTGDR -441C/T polymorphism showed Chi^{2} (χ ^{2})=0.29, OR=0.95, 95% CI (0.70-1.15) and p=0.599. Neither the genotypic nor the allelic frequencies observed for the PTGDR -441C/T polymorphism, were significantly associated with asthma or asthma phenotypes. Conclusions: The PTGDR -441C/T polymorphism is not associated with asthma or its phenotypes in the studied North Indian population. [ABSTRACT FROM AUTHOR]

Variants in genes involved in pancreatic β-cell development and function are known to cause monogenic forms of type 2 diabetes and are also associated with complex form. In this study, we studied the genetic association of polymorphisms in such important genes with type 2 diabetes in the high-risk Indians. We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. HNF4A promoter P2 polymorphisms rs1884613 and rs2144908, which are in high linkage disequilibrium, showed significant association with type 2 diabetes (odds ratio (OR)=1.37 (95% confidence interval (CI) 1.19-1.57), P=9.4 × 10−6 for rs1884613 and OR=1.37 (95%CI 1.20-1.57), P=6.0 × 10−6 for rs2144908), as previously shown in other populations. We observed body mass index-dependent association of these variants with type 2 diabetes in normal-weight/lean subjects. Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10−4). Thus, pancreatic β-cell development and function genes contribute to susceptibility to type 2 diabetes in North Indians. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Hypertension and dyslipidemia have been associated with cardiovascular disease (CVD). We investigated the association of candidate gene polymorphisms in angiotensin-converting enzyme (ACE) and cholesterol ester transfer protein (CETP) genes in a cohort of Asian Indian patients with and those without type 2 diabetes. Methods: PCR-based genotyping of insertion/deletion (I/D) polymorphism of ACE (rs4646994) and –629C>A of CETP (rs1800775) was carried out in 520 individuals, of whom 160 had CVD+type 2 diabetes mellitus (T2DM), 90 were CVD patients without T2DM, 150 had T2DM with no cardiovascular complications, and 120 were age- and sex-matched healthy controls. Results: With respect to the ACE gene I/D polymorphism, there was a higher percentage of D/D genotype in CVD+T2DM patients, but it was not statistically significant, while the CETP –629A allele was significantly associated with CVD+T2DM patients (P=.000007; odds ratio=0.46; 95% confidence interval=0.32–0.65) as compared with the normal controls and not with CVD alone. Additive interactions between the AA+I/I genotypes, AC+I/D genotypes, and AC+D/D were identified between the patients and the controls with P values of .0052, .0009, and .0078, respectively. Conclusions: Our study suggests that candidate gene polymorphism –629C>A of CETP may serve as a susceptibility biomarker for CVD in T2DM patients. Analyzing the combined effect of both ACE and CETP genotypes would enhance the sensitivity and specificity of CVD risk estimation in the T2DM patients in our population. [Copyright &y& Elsevier]

Abstract: Globally only 5–10% of people encountering Mycobacterium tuberculosis have a lifetime risk of active disease indicating a strong host genetic bias towards development of tuberculosis. In the current study we investigated genotype variants pertaining to five cytokine genes namely IFNG, TNFA, IL4, IL10 and IL12 in the north Indian population with active pulmonary tuberculosis (APTB) and correlated the serum cytokine levels with the corresponding genotypes. Twenty five single nucleotide polymorphisms (SNPs) including six loci examined for the first time in tuberculosis were selected for genotyping in 108 patients with APTB from north India and 48 healthy regional controls (HC). Applying exclusion criteria 12 SNPs passed all the filters and were analysed further. The serum cytokine concentrations were measured by ELISA. Compared to HC mean serum IFN-γ, IL-12, IL-4, and IL-10 levels were higher in APTB (p =0.3661, p =0.0186, p =0.003, p =0.7, respectively). In contrast the mean serum TNF-α level was higher in HC (p =0.007). Comparison of genotypes and serum levels of the corresponding cytokine genes reveal that though IFN-γ and IL-4 levels were higher in APTB the genotype variants showed no difference between HC and APTB. In contrast the genotypes of the selected rsIDs in the TNFA, IL12 and IL10 genes showed significant association with the varying serum levels of corresponding cytokines. The variant of the TNFA gene at rs3093662, the IL12 gene at rs3213094 and rs3212220 and the IL10 gene at rs3024498 did show a strong indication to be of relevance to the immunity to tuberculosis. To our knowledge this is the first report from this region relating genotypes and serum cytokine levels in north Indian population. [Copyright &y& Elsevier]

Objectives: Obesity is associated with high levels proinflammatory cytokines like tumour necrosis factor alpha (TNF-α), which may play an important role in the genesis of insulin resistance. We evaluated the relationship of -308G/A polymorphism of TNF-α gene with obesity and insulin resistance in Asian Indians in north India. Methods: This cross-sectional study included 151 apparently healthy individuals (79 males, 72 females) 18-50 yrs of age from New Delhi, India. Body composition by dual-energy x-ray absorptiometry (DEXA) and abdominal fat by magnetic resonance imaging (MRI) were measured. Biochemical measurements included OGTT, lipids, fasting insulin, hs-CRP and TNF-α levels. We analysed -308G/A polymorphism of TNF-α gene and studied its association with obesity and biochemical parameters. Results: At comparable BMI, abdominal obesity was more prevalent in females (50%) as compared to males (20%). The wild genotype (GG) was present in 78.8%, GA in 17.9%, and AA in 3.3% subjects. Measures of body composition, abdominal fat distribution, lipids, insulin, hs-CRP and TNF-α levels were not influenced by the presence of -308G/A polymorphism. Serum TNF-α levels correlated significantly with fasting insulin in both genders. Conclusion: TNF-α levels correlate with fasting insulin but not with indicators of body composition in Asian Indians. The -308G/A polymorphism of TNF-α gene is not associated with differences in the serum levels of TNF-α in Asian Indians. [ABSTRACT FROM AUTHOR]

Abstract: Several single nucleotide polymorphisms of the TP53 gene have been reported, amongst which polymorphism in codon 72 (rs1042522) has received significant attention and shown to be associated with disease susceptibility in different cancer types. However, there are variable reports on this polymorphism in gliomas from worldwide with inconsistent results. In addition, the implications of other polymorphic loci are not much explored in gliomas. Hence, in the present study the TP53 sequence was analyzed for all polymorphism and mutations in a total of 84 gliomas of different types and grades from patients of Indian origin. The complete sequence of all coding exons (2 to 11) and introns 2, 3, 5 and 8 of TP53 gene were studied while for introns 1, 4, 6, 7, 9 and 10, only exon flanking regions could be studied. The polymorphic loci were compared with control population. In addition to the well known codon 72 polymorphism (rs1042522), three other polymorphisms rs1642785, rs1800370 and a 16 base pair insertion in intron-3 were found. At codon 72, our study showed higher Arg/Arg genotype in gliomas compared to normal population (38% versus 13%). The Arg allele frequency in glioma patients was comparatively higher than controls (0.55 versus 0.45; P=0.037). The Arg allele frequency was also high in adult glioblastomas compared to paediatric counterparts (0.55 versus 0.36). However, there was no significant association of TP53 mutations with any genotype of codon 72. At rs1642785, the G allele frequency was significantly higher in gliomas than in control population (0.55 versus 0.36, P=0.005). The genotype at a 16 base pair insertion in intron-3 was almost similar in case and control. However, the polymorphism at rs1800370 was exclusive to gliomas. This is the first report of TP53 gene polymorphism in glioma patients from India. Our study also delineates the frequency of four polymorphisms in gliomas for the first time. The codon 72 variant (rs1042522) and rs1642785 polymorphisms possibly poses risk to glioma development in Indian population. However, the functional significance of these polymorphism needs further elucidation. [Copyright &y& Elsevier]

Background & objectives: Many pharmacologically-relevant polymorphisms show variability among different populations. Though limited, data from Caucasian subjects have reported several single nucleotide polymorphism (SNPs) in folate biosynthetic pathway. These SNPs may be subjected to racial and ethnic differences. We carried out a study to determine the allelic frequencies of these SNPs in an Indian ethnic population. Methods: Whole blood samples were withdrawn from 144 unrelated healthy subjects from west India. DNA was extracted and genotyping was performed using PCR-RFLP and Real-time Taqman allelic discrimination for 12 polymorphisms in 9 genes of folate-methotrexate (MTX) metabolism. Results: Allele frequencies were obtained for MTHFR 677T (10%) and 1298 C (30%), TS 3UTR 0bp (46%), MDR1 3435T and 1236T (62%), RFC1 80A (57%), GGH 401T (61%), MS 2756G (34%), ATIC 347G (52%) and SHMT1 1420T (80%) in healthy subjects (frequency of underlined SNPs were different from published study data of European and African populations). Interpretation & conclusions: The current study describes the distribution of folate biosynthetic pathway SNPs in healthy Indians and validates the previous finding of differences due to race and ethnicity. Our results pave way to study the pharmacogenomics of MTX in the Indian population. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians. Peroxisome proliferator activated receptor gamma2 (PPARγ2) has been implicated in adipocyte differentiation. Neuropeptide Y (NPY) is also considered as a candidate gene for excess body fat accumulation. The association of PPARγ2 (Pro12Ala)} and NPY (Leu7Pro) gene polymorphisms with OSA has not been studied in Asian Indians. Objective: To study the distribution of PPARγ2 (Pro12Ala) and NPY (Leu7Pro) polymorphism in Asian Indians with and without OSA. Methods and results: This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m^{2})]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses). PPARγ2 (Pro12Ala) and NPY (Leu7Pro) gene} polymorphisms were studied in all subjects. The frequency of the variant allele (Ala12) of PPARγ2 gene was significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; χ^{2}= 9.7; p = 0.001). The distribution of the variant allele (Pro7) of NPY gene was comparable in subjects with OSA (3.5%) and without OSA (3.6%; χ ^{2} = 0.001, p = 0.94). Conclusion: This study reveals a significantly higher frequency of PPARγ2 (Ala12) allele in obese Asian Indians with OSA when compared to obese Asian Indians without OSA. [ABSTRACT FROM AUTHOR]

Mannose-binding lectin (MBL) is a circulating pattern-recognition molecule involved in the innate immune system that mediates phagocytosis and activates complement by binding to carbohydrate motifs. MBL-2 allelic variants are associated with deficiencies in innate immunity and have been found to be correlated with human immunodeficiency virus (HIV) infection. The present study investigated the role of MBL-2 exon-1 gene polymorphism (A, B, C and D) in 180 HIV-1 seropositive (HSP) stratified on the basis of disease severity (stage I, II, III), 50 HIV-1 exposed seronegative (HES) and 305 HIV-1 seronegative (HSN) individuals as a possible factor in the susceptibility to HIV-1 infection and the influence on disease progression among North Indian individuals. In our population, gene frequencies of MBL-2 variants were 15%, 5% and 2% for B, C and D alleles, respectively. The frequency of A/O heterozygous genotype was higher (42.00%), mainly because of A/D in HES group compared with HSP (35.00%) and HSN (36.72%) group. Homozygous B/B genotype was more frequent in HSP (6.11%) group than in HSN (1.31%; P = 0.005; odds ratio (OR) = 4.898) and was significantly associated with fourfold risk of acquiring HIV-1 infection. Our findings indicate that homozygosity for the codon 54-allele associated with low MBL production in the exon-1 of the MBL-2 gene is associated with increased susceptibility to HIV-1 infection in the studied population. [ABSTRACT FROM AUTHOR]

Summary: We assessed the association of COX-2 polymorphisms at promoter sites −1195, −765 and at 3′UTR (8473) in 193 patients with oral squamous cell carcinoma (OSCC) and 137 normal subjects by PCR–RFLP. Although no significant difference was observed in the frequency of COX-2 −1195G>A, −765G>C and 8473C>T single nucleotide polymorphisms (SNPs) between patients and controls, COX-2 −1195G/A genotype showed higher while −765G/C and 8473C/T showed lower prevalence in patients as compared to normal subjects. Logistic regression analysis of these three polymorphisms revealed a quantitative risk associated with −1195G>A SNP (OR 3.07 at 95%CI) while −765G>C and 8473C>T appeared to be protective. Results of the present study indicate that these three functional variants in the COX-2 regulatory region may contribute to risk modification of tobacco-related oral squamous cell carcinoma in Asian Indians. [Copyright &y& Elsevier]

Abstract: The prevalence of thiopurine S-methyltransferase (TPMT) polymorphism and its association with clinical and hematological toxicities was retrospectively analyzed in 71 Indian children with acute lymphoblastic leukemia (ALL). Only heterozygous TPMT alleles were observed (10%, 7/71) with relative frequencies being *1/*3C (4.2%), *1/*2 (4.2%) and *1/*3A (1.4%). The median 6-mercaptopurine dose administered during the maintenance therapy was 31% lower among patients with heterozygous TPMT alleles versus the rest (32.1mg/m2/day and 46.2mg/m2/day, p =0.005), though the myelosuppression and toxicities were similar in both the groups. Identification of TPMT genotype appears to be important in making the ALL treatment more effective and less toxic. [Copyright &y& Elsevier]

Genetic polymorphisms in Toll-like receptor 4, TLR4 896 A/G (Asp299Gly) and 1196 C/T (Thr399Ile) have been reported to influence TLR4 function and the innate host immune response to mycobacteria. We investigated the effect of these single nucleotide polymorphisms on susceptibility and severity of pulmonary tuberculosis (PTB) in the Asian Indian population. A significantly increased frequency of TLR4 Asp299Gly mutation was observed in the patient group (17%) as compared with healthy controls [8.8%, χ2 = 10.7, P = 0.001,odds ratio (OR ) = 2.1]. On the other hand, the TLR4 Thr399Ile mutation occurred with comparable frequencies in the two groups (12.6% among patients and 9% in healthy controls). The PTB patients were categorized on the basis of their bacillary load as 3+, 2+, 1+, negative and on the extent of lung involvement as having minimal, moderate, and far-advanced lung disease. The 299Gly mutant occurred in homozygous state (GG) only in patients with high bacillary load (3+) and those with far-advanced lung disease. Similarly, the mutant 399Ile was significantly pronounced in these patients in the homozygous state (TT). The present data suggest that TLR4 substitutions at residues 299 and 399 are associated with pulmonary TB, particularly, the most severe disease. [ABSTRACT FROM AUTHOR]

Abstract: Ischemic stroke is a leading cause of death throughout the world. An increasing number of studies have suggested that genetic factors are important in the stroke risk. The aim of our study was to investigate whether the Variable Number of Tandem Repeats (VNTR) polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene is associated with ischemic stroke in a South Indian population. 357 patients and 283 controls were enrolled in this case–control study. The ischemic stroke patients were classified according to TOAST classification. The eNOS gene polymorphism was determined by polymerase chain reaction–polyacrylamide gel electrophoresis. The genotypes were confirmed by sequencing the PCR products. There were significant differences in the genotype and allele frequencies of eNOS polymorphism between the patients with ischemic stroke and healthy controls (p =0.000). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and eNOS gene variant revealed that the VNTR polymorphism in intron 4 of the eNOS gene is significantly [adjusted odds ratio=6.23, 95%CI (4.30–9.29), p =0.000] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We did not find significant association of this polymorphism with any specific stroke subtype. Further hypertensives bearing 4a allele in high frequency are more predisposed to stroke. [Copyright &y& Elsevier]

Abstract: Background: Endothelium derived nitric oxide is formed from l-arginine by endothelial nitric oxide synthase encoded by the nitric oxide synthase 3 (NOS3) gene. Nitric oxide possesses a variety of protective effects on endothelial cells and therefore NOS3 is a logical candidate gene to be investigated for the susceptibility of deep vein thrombosis (DVT). Methods: One hundred consecutive patients (M: F=56:44) with idiopathic deep vein thrombosis and an equal number of age and sex matched healthy controls were the study subjects. All study subjects were typed for five NOS3 polymorphisms (−786C/T, −922A/G, 894G/T, Intron 4 VNTR, and Intron 23 G10T). Results: Two polymorphisms (−922A/G and 894G/T) are showing their association with DVT. −922A/G shows both genotypic (P =0.0218; χ 2 =5.25; O.R=1.94) as well as allelic association (P =0.0014; χ 2 =10.19; O.R=2.0) while 894G/T shows only allelic (P =0.04; χ 2 =3.93; O.R=3.93) association with DVT. Conclusion: Susceptibility to DVT in North Indian Asian patients may be associated with some variants of NOS3 gene. [Copyright &y& Elsevier]

Background: Several studies hinted about the clustering of risk variables of the metabolic syndrome (MS) and suggested that the underlying genetic polymorphisms could be responsible for the increasing incidence of coronary heart disease (CHD) in people of Indian origin. Therefore, identification of the components of the MS along with the genetic factors could be one of the aspects to make an attempt to prevent the increasing incidence of CHD. Materials and Methods: Principal component factor analysis (PCFA) was undertaken to identify the components or factors of the MS among the adult (⩾30 years) Asian Indians living in and around Calcutta, India. The study comprised 350 adult Asian Indians. Anthropometric measurements were taken, and lipid profiles, blood pressure and fasting blood glucose were measured for each participant. Two genetic polymorphisms, namely, angiotensin converting enzyme (ACE) gene polymorphism (insertion/deletion [I/D]) or ACE (I/D) and apolipoproteinE (Hha I) were also studied. Results: PCFA revealed 3 factors that cumulatively explained 65.39% of the observed variance of the MS by measured variables. The 3 factors identified were lipids and lipoprotein (Factor 1), centripetal fat and blood pressure (Factor 2), and ACE (I/D) polymorphism with blood pressure (Factor 3). Moreover, the first 2 factors, that is, lipids, lipoprotein, centripetal fat, and blood pressures cumulatively explained ∼46% (45.94%) of the observed variance of MS in this population. Conclusions: Since more than 1 factor was identified for the MS phenotype, more than 1 physiogenetic mechanism could be accounted for MS in the Asian Indian population. [ABSTRACT FROM AUTHOR]

Background and Aims: Chemokines and transcription factor NF-κB play a pivotal role in development of carcinoma of the bladder (CaB). The present study was conducted to analyze the association of chemokines IL-8 −251 T>A and +678 C>T and NF-κB −94 (ATTG) insertion/deletion polymorphisms with the risk of CaB and outcome after bacillus Calmette-Guerin (BCG) immunotherapy in a cohort of northern India. Methods: Histologically confirmed 205 CaB cases and 270 controls were included. Of these, 71 patients were treated with BCG immunotherapy. Genotyping was done using allele-specific PCR methodology. Results: The variant genotype (AA) of IL-8 −251 polymorphism was associated with more than 2-fold risk of CaB (OR 2.12; p = 0.003; 95% CI 1.28–3.52). None of the other genotypes showed association with CaB risk. Subsequently, the diplotype −251A/+678T demonstrated a 1.8-fold increased risk for CaB (OR 1.84, 95% CI 1.37–2.47). Furthermore, −251 AA genotypes reduced the risk of recurrence after BCG immunotherapy (AA; HR 0.12; 95% CI 0.04–0.41). Subsequently, improved recurrence-free survival (mean recurrence-free survival for GG, GA and AA genotypes was 24, 39 and 53 months respectively). Similarly, NF-κB ATTG Ins/Ins genotype was at reduced risk of recurrence after BCG treatment compared to Del/Del genotype, which exhibited a 2.5-fold increased risk of recurrence in patients treated with BCG immunotherapy (HR, 2.53; 95% CI 1.00–6.36). Subsequently, mean recurrence-free survival (Ins/Ins, 41; Ins/Del, 44 and Del/Del, 10 months; log rank, 0.030). Conclusions: Our results suggested that the IL-8 −251T>A polymorphism may be a relevant host susceptibility factor for bladder carcinoma development and may influence outcome after BCG immunotherapy. Similarly, NF-κB ATTG polymorphism may also modify risk-free survival of BCG-treated patients. [Copyright &y& Elsevier]