Polymorphisms in Four Genes (KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963) and Their Correlation with Type 2 Diabetes Mellitus in Han Chinese in Henan Province, China.

Genetic variants at KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963 have been associated with type 2 diabetes mellitus (T2DM), but the results are contradictory in Chinese populations. The aim of the present study was to investigate the association of these four SNPs with T2DM in a large population of Han Chinese at Henan province, China. Seven-hundred-thirty-six patients with T2DM (cases) and Seven-hundred-sixty-eight healthy glucose-tolerant controls were genotyped for KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963. The association of genetic variants in these four genes with T2DM was analyzed using multivariate logistic regression. Genotypes and allele distributions of KCNQ1 rs151290 were significantly different between the cases and controls (p < 0.05). The AC and CC genotypes and the combined AC + CC genotype of rs151290 in KCNQ1 were associated with increases risk of T2DM before (OR = 1.482, 95% CI = 1.062-2.069; p = 0.021; OR = 1.544, 95% CI = 1.097-2.172, p = 0.013; and OR = 1.509, 95% CI = 1.097-2.077, p = 0.011, respectively) and after (OR = 1.539, 95% CI = 1.015-2.332, p = 0.042; OR = 1.641, 95% CI = 1.070-2.516, p = 0.023; and OR = 1.582, 95% CI = 1.061-2.358, p = 0.024; respectively) adjustment for sex, age, anthropometric measurements, biochemical indexes, smoking and alcohol consumption. Consistent with results of genotype analysis, the C allele of rs151290 in KCNQ1 was also associated with increased risk of T2DM (OR = 1.166, 95% CI = 1.004-1.355, p = 0.045). No associations between genetic variants of KLF14 rs972283, GCKR rs780094 or MTNR1B rs10830963 and T2DM were detected. The AC and CC genotypes and the C allele of rs151290 in KCNQ1 may be risk factors for T2DM in Han Chinese in Henan province.

Association of LRP5, TCF7L2, and GCG variants and type 2 diabetes mellitus as well as fasting plasma glucose and lipid metabolism indexes.

Recent data puts WNT signaling pathway in a pivotal role in regulating pancreas development as well as islet function, insulin production and secretion. The key effectors in the WNT signaling pathway are low-density lipoprotein receptor-related protein 5 (LRP5), transcription factor 7-like 2 (TCF7L2), and downstream-regulated glucagon (GCG). Our previous studies suggest that the WNT signaling pathway plays a significant role in risk of type 2 diabetes mellitus (T2DM) in Chinese population. The main purpose of the present study was to investigate the associations of single nucleotide polymorphisms (SNPs) in LRP5, TCF7L2 and glucagon (GCG) and quantitative traits in a healthy population. We used tag SNP to screen candidate SNPs for LRP5 and GCG; for TCF7L2, used the confirmed SNP rs11196218. A total of 1842 patients with T2DM and 7777 healthy controls underwent genotyping for the SNPs. We found a significant association of rs3758644 in LRP5 and fasting plasma glucose (p=0.006), and rs11196218 in TCF7L2 and triglycerides level (p=0.004). Among the SNPs in LRP5, TCF7L2, and GCG analyzed, only rs3758644 of LRP5 and rs11196218 of TCF7L2 were significantly associated with fasting plasma glucose and triglycerides index, respectively, in a healthy population.

Glucagon gene polymorphism modifies the effects of smoking and physical activity on risk of type 2 diabetes mellitus in Han Chinese.

Few genome-wide association studies have considered interactions between multiple genetic variants and environmental factors associated with disease. The interaction was examined between a glucagon gene (GCG) polymorphism and smoking, alcohol consumption and physical activity and the association with risk of type 2 diabetes mellitus (T2DM) in a case-control study of Chinese Han subjects. The rs12104705 polymorphism of GCG and interactions with environmental variables were analyzed for 9619 participants by binary multiple logistic regression. Smoking with the C-C haplotype of rs12104705 was associated with increased risk of T2DM (OR=1.174, 95% CI=1.013-1.361). Moderate and high physical activity with the C-C genotype was associated with decreased risk of T2DM as compared with low physical activity with the genotype (OR=0.251, 95% CI=0.206-0.306 and OR=0.190, 95% CI=0.164-0.220). However, the interaction of drinking and genotype was not associated with risk of T2DM. Genetic polymorphism in rs12104705 of GCG may interact with smoking and physical activity to modify the risk of T2DM.

Association of the rs11196218 polymorphism in TCF7L2 with type 2 diabetes mellitus in Asian population.

OBJECTIVE: To clarify the association of rs11196218 polymorphism in transcription factor 7-like 2 (TCF7L2) and type 2 diabetes mellitus (T2DM) in Asian population by a case-control study and meta-analysis. METHODS: In the case-control study, 1842 patients with T2DM and 7777 normal glucose-tolerant controls in the Henan province of China were genotyped for rs11196218 in TCF7L2 by PCR-ligase detection reaction. We used allele, co-dominant, dominant and recessive models to evaluate the risk association and performed a meta-analysis of the results of different genetic models in previous studies and the current study. RESULTS: The AG genotype of rs11196218 was associated with risk of T2DM in the Henan population (odds ratio 1.37, 95% confidence interval 1.06-1.78), and dominant model showed marginal significant association (1.28, 0.99-1.67). Meta-analysis of 10 studies revealed the dominant model associated with T2DM in the overall population (1.20, 1.05-1.36). When stratified by region (southern and northern China and Japan), both the AG genotype and the dominant model were associated with risk of T2DM in southern Chinese (1.31, 1.03-1.66; 1.27, 1.01-1.60, respectively). CONCLUSION: The rs11196218 polymorphism in TCF7L2 is associated with risk of T2DM in Asian population.

Association of rs12255372 in the TCF7L2 gene with type 2 diabetes mellitus: a meta-analysis.

Our objective was to evaluate the association of rs12255372 in the TCF7L2 gene with type 2 diabetes mellitus (T2DM) in the world population. We carried out a survey of the literature about the effect of rs12255372 on genetic susceptibility to T2DM by consulting PubMed, the Cochrane Library, and Embase from 2006 to 2012, and then performed a meta-analysis of all the studies in order to evaluate the association between rs12255372 and T2DM. A total of 33 articles including 42 studies (with 34,076 cases and 36,192 controls) were confirmed to be eligible and were included in the final meta-analysis: 6 studies conducted on Europeans, 14 on Caucasians, 17 on Asians, 2 on Africans, and 3 on Americans. Overall, the effect size was as follows: for the variant allele T (OR = 1.387, 95%CI = 1.351-1.424), for the TT genotype (OR = 1.933, 95%CI = 1.815-2.057), for the GT genotype (OR = 1.363, 95%CI = 1.315-1.413), for the dominant model (OR = 1.425, 95%CI = 1.344-1.510), and for the recessive model (OR = 1.659, 95%CI = 1.563-1.761). In summary, by pooling all available qualified data from genetic studies on rs12255372 and T2DM, we have confirmed that rs12255372 is significantly associated with susceptibility to T2DM in the global population.

Association of rs12255372 in the TCF7L2 gene with type 2 diabetes mellitus: a meta-analysis

Our objective was to evaluate the association of rs12255372 in the TCF7L2 gene with type 2 diabetes mellitus (T2DM) in the world population. We carried out a survey of the literature about the effect of rs12255372 on genetic susceptibility to T2DM by consulting PubMed, the Cochrane Library, and Embase from 2006 to 2012, and then performed a meta-analysis of all the studies in order to evaluate the association between rs12255372 and T2DM. A total of 33 articles including 42 studies (with 34,076 cases and 36,192 controls) were confirmed to be eligible and were included in the final meta-analysis: 6 studies conducted on Europeans, 14 on Caucasians, 17 on Asians, 2 on Africans, and 3 on Americans. Overall, the effect size was as follows: for the variant allele T (OR = 1.387, 95%CI = 1.351-1.424), for the TT genotype (OR = 1.933, 95%CI = 1.815-2.057), for the GT genotype (OR = 1.363, 95%CI = 1.315-1.413), for the dominant model (OR = 1.425, 95%CI = 1.344-1.510), and for the recessive model (OR = 1.659, 95%CI = 1.563-1.761). In summary, by pooling all available qualified data from genetic studies on rs12255372 and T2DM, we have confirmed that rs12255372 is significantly associated with susceptibility to T2DM in the global population.

Association of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) polymorphisms in TCF7L2 with type 2 diabetes in 9,619 Han Chinese population.

AIMS: We aimed to replicate the association of the rs290487 (IVS3C/T) and rs7903146 (IVS3C/T) polymorphisms of transcription factor 7-like 2 (TCF7L2) and type 2 diabetes mellitus (T2DM) in Han Chinese people in Henan province, China. METHODS: In all, 1,842 patients with T2DM and 7,777 normal glucose-tolerant controls underwent genotyping for the T2DM-associated variants rs7903146 (IVS3C/T) and rs290487 (IVS3C/T). W performed a meta-analysis of the association of the risk alleles of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) in TCF7L2 and T2DM in Han Chinese by combining previous studies with the present study. RESULTS: We found that T2DM was associated with the CC genotype (1.364, 1.137-1.636, p  = 0.001), the recessive model (1.457, 1.156-1.838, p  = 0.001) of rs290487 (IVS3C/T) and haplotype CC (1.116, 1.034-1.204, p  = 0.004) in Han Chinese. Moreover, our meta-analyses supported the association of the T allele (IVS3C/T) of rs7903146 (1.36, 1.24-1.48; p  = 6.404×10(-12)) and T2DM but not the C allele of rs290487 (IVS3C/T) (0.99, 0.85-1.15, p  = 0.890) in Han Chinese. We found no interactions between behavioral risk factors (smoking, alcohol drinking, and physical activity) and rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) polymorphisms. CONCLUSIONS: The CC genotype and the recessive model of the variant rs290487 (IVS3C/T) and CC haplotype of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) in TCF7L2 may be associated with T2DM in Han Chinese people in Henan province, China.