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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]

Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type 2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (−11377C→G and −11282T→C), one intronic SNP (+10211T→G) and one exonic SNP (+45T→G) by SSCP and direct sequencing in a pilot study ( n = 500). The +10211T→G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed that subjects with TG genotype of +10211T→G had significantly higher risk for diabetes compared to TT genotype [Odds ratio 1.28; 95% Confidence Interval (CI) 1.07–1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype ( P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was 1.53 (95%CI 1.3–1.8; P < 10−7) and that for GG genotype, 2.10 (95% CI 1.3–3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG ( P = 0.007) and TG ( P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T→G polymorphism in the first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia. [ABSTRACT FROM AUTHOR]

Abstract: One thousand thirty-eight normal glucose-tolerant and 1031 type 2 diabetic subjects selected from the Chennai Urban Rural Epidemiology Study were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay to investigate the association of rs12255372(G/T) and rs7903146(C/T) polymorphisms of the transcription factor 7–like 2 (TCF7L2) gene with type 2 diabetes mellitus in Asian Indians. The frequency of the “T” allele of both rs12255372(G/T) and rs7903146(C/T) polymorphisms was significantly higher in diabetic subjects (23% and 33%) compared to that in normal glucose-tolerant subjects (19% and 28%; P = .001 and P = .0001, respectively). Logistic regression analysis of the rs12255372(G/T) polymorphism showed that the odds ratio (adjusted for age, sex, and body mass index) was 1.56 (95% confidence interval [CI], 1.03-2.37; P = .034) for the TT genotype and 1.29 (95% CI, 1.06-1.58; P = .011) for the TG genotype when compared with the GG genotype. Adjusted odds ratios for the TT and TC genotypes of the rs7903146(C/T) polymorphism were found to be 1.50 (95% CI, 1.08-2.08; P = .013) and 1.44 (95% CI, 1.18-1.76; P = .0003), respectively, compared with the CC genotype. Normal glucose-tolerant subjects with the TT genotype of rs12255372(G/T) had significantly higher 2-hour plasma glucose levels (mean ± SD, 6.1 ± 1.4 mmol/L) than those with the GG genotype (5.6 ± 1.0 mmol/L, P = .011). Normal glucose-tolerant subjects with the TT genotype of rs7903146(C/T) polymorphism had significantly higher 2-hour plasma glucose levels (mean ± SD, 6.0 ± 1.3 mmol/L) than those with the CC genotype (5.6 ± 1.0 mmol/L, P = .004). In conclusion, the T allele of the rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene confer susceptibility to type 2 diabetes mellitus in Asian Indians. [Copyright &y& Elsevier]

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]

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]

Aim of Study: Endothelial dysfunction is a feature of cardiovascular disease, hypertension, dyslipidaemia and smoking, all of which are associated with diabetes induced nephropathy. The Cytokines have also found to play an important role in development of Diabetic nephropathy. Cytokines like monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation and normal T cell expressed and secreted (RANTES) and their receptors CCR2 and CCR5 mediate macrophage infiltration into kidney whose over-expression leads to glomerulosclerosis and interstitial fibrosis. We investigated the association of three single nucleotide polymorphisms (SNPs) and three insertion deletion polymorphisms from CCR5, MCP-1 and endothelial nitric oxide synthase (eNOS) genes among 400 type 2 diabetic individuals with (DNP) and without nephropathy (DMT2). Materials and Methods: Genotyping of the Insertion/Deletion polymorphisms was performed by PCR whereas the SNPs were genotyped by the PCR-RFLP assay, followed by agarose gel electrophoresis. The serum nitric oxide and hs-CRP levels were also assessed. Results: The prevalence of the MCP-1 I/I (AGCTCCTCCTTCTC/AGCTCCTCCTTCTC) homozygotes was significantly higher among DNP than among DMT2 group (P<0.0001, OR: 2.19, 95% CI: 1.4-3.2), however frequency of both the alleles of MCP-1-2518 A> G promoter polymorphism did not vary significantly between the two groups. The frequency of D allele (CCR5 delta I/D) and DD genotype was significantly higher in DNP than among DMT2 patients (D allele: P=0.001, OR: 2.59, 95% CI: 1.4-4.6; DD genotype: P<0.0001, OR: 3.1, 95% CI: 2.1-4.6). The variant genotype (CO, II, and TT) frequencies of all the three eNOS polymorphisms (-786 T>C, Intron 4 I/D, and 1917 G > T) differed significantly (P< 0.05) between the two groups. The hsCRP levels were higher in DNP (2.15±2.0 mg/L; P<0.05) as compared to DMT2 group (1.89±1.7 mg/L; P<0.05), but were statistically non-significant. The NO levels of DNP group (0.4±0.04 nmol/L) were significantly lower as compared to DMT2 group (0.75±0.18 nmol/L). Conclusion: Although hs-CRP levels were increased in diabetic patients, no direct association of the increased hs-CRP levels was observed with DNE Also, this study reveals an association of CCR5 delta (32 bp I/D), and MCP-1 gene I/D, eNOS -786 T> C promoter, Intron 4 I/D and 1917 G>T polymorphisms, but not MCP-1 gene promoter polymorphism (-2518 A>G) with the development of type 2 DNP among North Indians. [ABSTRACT FROM AUTHOR]