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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]

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: 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]

The association between two functional polymorphisms in alcohol dehydrogenase (ADH2/ADH1B) and aldehyde dehydrogenase (ALDH2) genes and alcohol dependence was examined in 182 Chinese and Indian patients undergoing treatment for alcohol dependence and 184 screened control subjects from Singapore. All subjects were screened by the Alcohol Use Disorders Identification Test (AUDIT). Patients were also administered the Severity of Alcohol Dependence Questionnaire (SADQ). Polymorphisms were genotyped by allele-specific polymerase chain reaction and selected genotypes confirmed by DNA sequencing or restriction fragment length polymorphism. Our results showed that frequencies of ADH1B**2 and ALDH2**2 were higher in controls compared to alcohol-dependent subjects for both Chinese and Indians. Frequencies of these two alleles were also higher in the 104 Chinese controls compared to the 80 Indian controls. None of the eight Chinese who were homozygous for both protective alleles was alcohol dependent. The higher frequencies of the protective alleles could explain the lower rate of alcohol dependence in Chinese. [ABSTRACT FROM AUTHOR]

Abstract: Background: Polymorphisms in cholesteryl ester protein gene have been linked to risk of coronary heart disease (CHD) in many world populations through their effect on reverse cholesterol transport. Methods: Five hundred four (504) unrelated electrocardiograph confirmed cases of CHD and 338 population based controls, matched by age and gender, belonging to the Tamilian population of south India were genotyped for polymorphisms in CETP gene using PCR RFLP methods. Results: The multivariate logistic regression analyses demonstrated that CETP B1B1 and CA genotypes of TaqIB and −629C>A were significantly associated with increased risk for CHD (odds ratio (OR) 2.7; 95% confidence intervals (CI) (1.5–3.3); OR 1.5 (1.1–2.4)) respectively. Combined wild genotypes of CETP gene showed an association with CHD (OR–1.7 (1.0–2.9) as well as the combined heterozygous mutants (OR 1.5 (1.0–2.3); p–0.03). Subgroup analysis based on gender revealed that men harboring CETP B1B1 and CA genotypes have a significant risk for CHD B1B1- 2.7 (1.7–4.3), CA-1.8 (1.3–2.6). There was no link between CETP I450V polymorphism and CHD. Analysis based on hypertensive status showed a significant association between these polymorphisms and non hypertensive CHD patients. Conclusions: The risk in non hypertensive and male CHD patients is higher in the presence of CETP B1B1 and CA genotypes. [Copyright &y& Elsevier]

Purpose: To investigate the relationship of apolipoprotein E (apoE) genotype, plasma levels of apoE and lipids in temporal lobe epilepsy (TLE) patients in Asian Indians. Status of plasma levels of Apo E in epilepsy patients has not been reported till date. Methods: ApoE gene polymorphism was analyzed in 58 patients with temporal lobe epilepsy (TLE) and 57 age and sex approximated controls using Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Levels of plasma apoE and lipids were measured using ELISA and enzymatic kits respectively. Results: The distribution of ApoE genotype in epilepsy patients and controls was comparable. Higher levels of plasma ApoE were observed in TLE patients as compared to controls (p=0.0001). Individuals with plasma levels of apoE > 190 mg/L were at 20 times higher odds (95%CI=2.46–163.34, p=0.005), while those with levels of apoE between 150–190 mg/L were at 4.9 times higher odds (95% CI=1.85–13.9, p=0.001), to develop TLE. Conclusions: We have observed for the first time, high levels of plasma apoE in epilepsy patients. The findings of this case-control study suggest that apolipoprotein E may play an important role in epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Thrombospondin 1 and 2 are multidomain calcium-binding extracellular glycoproteins and they play a role in platelet aggregation, inflammatory response and assembly of connective tissue extracellular matrix. The association of thrombospondins (TSP) in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) is well established. The association of the TSP-1 (Asn700Ser, 2210A→G, rs2228262) and TSP-2 un-translated region (UTR) (3949T→G, rs8089) gene variations among South Indian CAD and MI patients has been examined in the present study. Materials and Methods: We analyzed the thrombospondin polymorphisms in unrelated CAD patients (n=511) and a subgroup with an event of MI (n=173) compared with controls (n=522). The polymorphisms were assessed using polymerase chain reaction, restriction fragment length analysis and the circulating TSP concentration were measured using enzyme linked immune-sorbent assay. Results: The prevalence of TSP-1 and TSP-2 alleles did not show any significant difference statistically, when compared controls against CAD/MI patients. The rare GG genotype of the N700S polymorphism was not observed among the studied population. Further, multiple regression analysis revealed that there was no significant risk for CAD (OR=1.68; 95% CI 0.927 - 3.055; p=0.087) or MI (OR=1.84; 95% CI 0.846 - 4.007; p=0.124) for the GA genotype. The GA genotype showed no impact on clinical characteristics of the CAD patients and their circulating TSP-1 levels. A similar non-association was observed for the TSP-2 in 3949T→G polymorphism (GG genotype) for CAD (OR=0.64; 95% CI 0.278 - 1.455; p=0.636) and MI (OR=0.53; 95% CI 0.166 - 1.675; p=0.278). Conclusions: Our data suggests that the presence of thrombospondin-1 (rs2228262) and thrombospondin-2 (rs8089) variants need not be considered a risk for coronary artery disease or myocardial infarction among South Indians. [Copyright &y& Elsevier]