Association study of the single nucleotide polymorphisms in adiponectin-associated genes with type 2 diabetes in Han Chinese.
ABSTRACT Single-nucleotide polymorphisms (SNPs) of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus (T2DM), but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs of ADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects. rs16861194 (-11426 A>G) in the putative promoter of ADIPOQ was associated with T2DM (P = 0.007; OR = 1.29, 95%CI 1.08-1.55). None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.
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ABSTRACT: Diabetes is a serious global health problem. Large-scale genome-wide association studies identified loci for type 2 diabetes mellitus (T2DM), including adiponectin (ADIPOQ) gene and transcription factor 7-like 2 (TCF7L2), but few studies clarified the effect of genetic polymorphisms of ADIPOQ and TCF7L2 on risk of T2DM. We attempted to elucidate association between T2DM and polymorphic variations of both in Taiwan's Chinese Han population, with our retrospective case-control study genotyping single nucleotide polymorphisms (SNPs) in ADIPOQ and TCF7L2 genes both in 149 T2DM patients and in 139 healthy controls from Taiwan. Statistical analysis gauged association of these polymorphisms with risk of T2DM to show ADIPOQ rs1501299 polymorphism variations strongly correlated with T2DM risk (P = 0.042), with rs2241766 polymorphism being not associated with T2DM (P = 0.967). However, both polymorphisms rs7903146 and rs12255372 of TCF7L2 were rarely detected in Taiwanese people. This study avers that ADIPOQ rs1501299 polymorphism contributes to risk of T2DM in the Taiwanese population.TheScientificWorldJournal. 01/2014; 2014:650393.
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ABSTRACT: Background/objectives:To investigate the association of adiponectin and its gene polymorphisms with metabolic syndrome (MetS) and cardiovascular disease (CVD) risk factors in Chinese adolescents.Subjects/methods:This cross-sectional study enrolled 919 healthy middle school students (aged 11-16 years; 46.7% females). All participants underwent anthropometric and biochemical examinations, and MetS was diagnosed using 2007 International Diabetes Federation criteria. The presence of adiponectin and its genotypes of single nucleotide polymorphisms (SNPs) rs266729 (-11377C/G), rs2241766 (+45T/G) and rs1501299 (+276G/T) was detected.Results:(1) Serum adiponectin levels were negatively correlated with numerous CVD risk factors (all P<0.05), and following adjustments for confounding factors, a lower adiponectin level was an independent risk factor for MetS (odds ratio=5.59; 95% confidence interval: 1.90, 16.41). Central obesity and low levels of high-density lipoprotein cholesterol were positively associated with MetS and reduced serum adiponectin levels. (2) The genotype and frequencies of SNP-11377 and SNP+276 in a MetS group and non-MetS group were not significantly different. Subjects with genotype SNP+45 GG were at higher risk for MetS compared with subjects with genotypes SNP+45 TT (P=0.033) or TT+TG (P=0.021). Subjects with genotype SNP+276 TT or TT+TG had higher levels of serum adiponectin compared with subjects with SNP+276 GG (P=0.012 and 0.014, respectively).Conclusions:Adiponectin may be used as a predictive biomarker of MetS, and shows a significant association with CVD risk factors in Chinese adolescents. Adiponectin gene polymorphisms are associated with serum adiponectin concentrations and the presence of MetS.European Journal of Clinical Nutrition advance online publication, 30 July 2014; doi:10.1038/ejcn.2014.152.European journal of clinical nutrition. 07/2014;
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ABSTRACT: Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes but its causal role remains controversial. We used a Mendelian randomisation approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics based genetic risk scores to test the associations with gold standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 cases and 64,731 controls). In conventional regression analyses a 1 SD decrease in adiponectin levels was correlated with a 0.31 SD (95%CIs: 0.26-0.35) increase in fasting insulin, a 0.34 SD (0.30-0.38) decrease in insulin sensitivity and a type 2 diabetes odds ratio of 1.75 (95%CIs: 1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD, 95%CI: -0.07, 0.11, N=29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95%CIs: -0.38, -0.02; N=1,860) and no evidence of a relationship with type 2 diabetes (odds ratio 0.94; 95%CIs: 0.75, 1.19; N= 2,777 cases and 13,011 controls). Using the ADIPOQ summary statistics genetic risk scores we found no evidence of an association between adiponectin lowering alleles and insulin sensitivity (effect per weighted adiponectin lowering allele: -0.03 SD, 95%CIs: -0.07, 0.01; N=2,969) or type 2 diabetes (odds ratio per weighted adiponectin lowering allele: 0.99; 95%CIs: 0.95, 1.04; 15,960 cases vs. 64,731 controls). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes.Diabetes 07/2013; · 7.90 Impact Factor