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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]

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]

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]

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]

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]

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]

Objective:To investigate the association of insulin receptor substrate-2 (IRS-2) G1057D polymorphism with type 2 diabetes and obesity in Asian Indians.Methods:The study comprised of 1193 normal glucose tolerant (NGT) subjects and 1018 subjects with type 2 diabetes, aged 20 years with an average body mass index of 23.7±4.6 and 25.3±4.2 kg/m2, respectively. The subjects were unrelated and randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), a population-based study in Chennai in southern India. The G1057D polymorphism of the IRS-2 gene was genotyped using PCR-RFLP assay.Results:The genotype frequency of the IRS-2 G1057D polymorphism was significantly different between the NGT and type 2 diabetic groups (P=0.0007) in the total study subjects and among the obese subjects (P=0.00007). Logistic regression analysis showed that the DD genotype showed an increased susceptibility to diabetes with an odds ratio (adjusted for age and sex) of 2.19 (95% CI: 1.34–3.57, P=0.002) when compared to the GG+GD genotype, among the obese subjects, but not in non obese subjects. In order to explore possible interaction with obesity, logistic regression analysis was performed and the coefficient corresponding to the interaction parameter (genotype × obesity) was significant (P=0.0001).Conclusion:In Asian Indians, the DD genotype increases susceptibility to type 2 diabetes by interacting with obesity.International Journal of Obesity (2007) 31, 97–102. doi:10.1038/sj.ijo.0803356; published online 25 April 2006 [ABSTRACT FROM AUTHOR]

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]

Objective:To evaluate whether polymorphisms in the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A) gene were related to body fat in Asian Indians.Methods:Three polymorphisms of PPARGC1A gene, the Thr394Thr, Gly482Ser and +A2962G, were genotyped on 82 type 2 diabetic and 82 normal glucose tolerant (NGT) subjects randomly chosen from the Chennai Urban Rural Epidemiology Study using PCR-RFLP, and the nature of the variants were confirmed using direct sequencing. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies using an expectation–maximization algorithm. Visceral, subcutaneous and total abdominal fat were measured using computed tomography, whereas dual X-ray absorptiometry was used to measure central abdominal and total body fat.Results:None of the three polymorphisms studied were in LD. The genotype (0.59 vs 0.32, P=0.001) and allele (0.30 vs 0.17, P=0.007) frequencies of Thr394Thr polymorphism were significantly higher in type 2 diabetic subjects compared to those in NGT subjects. The odds ratio for diabetes (adjusted for age, sex and body mass index) for the susceptible genotype, XA (GA+AA) of Thr394Thr polymorphism, was 2.53 (95% confidence intervals: 1.30–5.04, P=0.009). Visceral and subcutaneous fat were significantly higher in NGT subjects with XA genotype of the Thr394Thr polymorphism compared to those with GG genotype (visceral fat: XA 148.2±46.9 vs GG 106.5±51.9 cm2, P=0.001; subcutaneous fat: XA 271.8±167.1 vs GG 181.5±78.5 cm2, P=0.001). Abdominal (XA 4521.9±1749.6 vs GG 3445.2±1443.4 g, P=0.004), central abdominal (XA 1689.0±524.0 vs GG 1228.5±438.7 g, P<0.0001) and non-abdominal fat (XA 18763.8±8789.4 vs GG 13160.4±4255.3 g, P<0.0001) were also significantly higher in the NGT subjects with XA genotype compared to those with GG genotype. The Gly482Ser and +A2962G polymorphisms were not associated with any of the body fat measures.Conclusion:Among Asian Indians, the Thr394Thr (G → A) polymorphism is associated with increased total, visceral and subcutaneous body fat.International Journal of Obesity (2006) 30, 884–891. doi:10.1038/sj.ijo.0803228; published online 31 January 2006 [ABSTRACT FROM AUTHOR]

Aims The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G, of the peroxisome proliferator activated receptor-γ co-activator-1 alpha (PGC-1α) gene with Type 2 diabetes in Asian Indians. Methods The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Haplotype frequencies were estimated using an expectation–maximization (EM) algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of the Type 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) ( P = 0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) ( P = 0.002). Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals: 1.264–2.241, P = 0.0004). Age adjusted glycated haemoglobin ( P = 0.003), serum cholesterol ( P = 0.001) and low-density lipoprotein (LDL) cholesterol ( P = 0.001) levels and systolic blood pressure ( P = 0.001) were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms. Conclusions The A allele of Thr394Thr (G → A) polymorphism of the PGC-1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population. [ABSTRACT FROM AUTHOR]

The association between apolipoprotein E (apo E) polymorphism and stroke has been controversial. So far there are no studies reported on the polymorphism of apolipoprotein E in cerebrovascular diseases in the Asian Indians. A blinded case–control study was therefore undertaken and the apo E genotypes and lipid profile of a total of 120 subjects (63 stroke patients and 57 healthy controls) were done. The frequency distribution of apo E alleles and genotypes were assessed and their relation with the occurrence of stroke in Asian Indian subjects was determined. A significantly high frequency of apo ε4 allele (30%) was observed in the stroke patients than the controls (11%) (p < 0.005), and patients with ε4 allele had a fourfold higher odds to develop stroke OR (95%CI) 4.2 (1.8–10.1) (p < 0.005). On multivariate analysis, after adjusting for age, triglycerides and hypertension, the association of ε4 allele with stroke was found to be no longer statistically significant, OR (95%CI) 1.2 (0.4–4.5) (p = NS). On multiple logistic regression analysis age, OR (95%CI) 1.1 (1.1–1.2) (p < 0.001), and hypertension OR (95%CI) 15.1 (2.6–89.1) (p < 0.005) were found to be independent risk factors for development of stroke. This is the first report to have examined the association of apo E gene polymorphism with stroke in the Asian Indians. This study suggests that apo ε4 allele, triglycerides, age and hypertension are the predictors for stroke development. [ABSTRACT FROM AUTHOR]

Abstract: A total of 350 (184 males and 166 females) adults participated in the study. A sample of 138 individuals was selected randomly for genotyping. The synergistic effect of ACE (I/D) and ApoE (HhaI) on metabolic syndrome (MS) showed that individuals with e4/4+D/D combination had the highest occurrence of metabolic abnormalities. [Copyright &y& Elsevier]