Relationships Of Rs13266634 And Rs11196218 Polymorphisms In SLC30A8 (Solute Carrier Family 30, Member 8) And TCF7L2 (Transcription Factor 7 Like 2) Gens With Type 2 Diabetes In Southern Chinese Han Population

Type 2 diabetes mellitus(T2DM) is a complicated heterogeneous disease.The main pathophysiology is insulin in periphery tissue which would cause decreased glucose utilization combined with decliningβ-cell function.In the present study,we aimed to identify the association of insulin related gene with T2DM by investigating genetic poly-morphisms.Transcription factor 7 like-2(TCF7L2) is by far the strongest type 2 diabetes susceptibility gene to type 2 diabetes to date.Genetic variants in TCF7L2 possibly altering expressing of TCF7L2 in pancreatic islets confer a strong risk of type 2 diabetes.As a component of the bipartite transcription factorβ-catenin/TCF,TCF7L2 is involved in conveying Wnt signaling gene expression during adulthood.This transcriptional regulator has been shown to be involved in stimulating the proliferation of pancreaticβ-cells and the production of the incretin hormone glucagon-like peptide-1(GLP-1) in intestinal endocrine L cells.SLC30A8 gene encodes aβ-cell specific ZnT-8 protein,it modulates the biosynthesis,stabilization and storage of insulin through transporting Zn into secretary vesicles of theβcell.Recently,A genome wide association study(GWAs) from the Occident population indicated that:The rs13266634 polymorphism in SLC30A8 could raise the risk of type 2 diabetes. For different races have different genetic background and living enviroment,the genes reported having associations with disease in different races would make contribution to human complex diseases in future studies.The purpose of this study is to investigate the frequency distribution of SNPs and haplotype in SLC30A8,TCF7L2 genes for the Chinese Han people living in the south.From probing into the relations between the two genes and type 2 diabetes, accumulating the information of the SNPs for Chinese Han people which could be beneficial to the research on the pathogenesis of type 2 diabetes.Objective:To study the single nucleotide polymorphisms of rs13266634 and rs11196218(the genotypes and the frequency)in SLC30A8 and TCF7L2 genes and their associations with type 2 diabetes,so as to probe into the involvement of SLC30A8 and TCF7L2 in the etiology of type 2 diabetes(T2DM).Methods:The rs13266634 and rs11196218 polymorphisms of SLC30A8 and TCF7L2 genes were genotyped in 459 Han nationalities living around Shanghai,including 259 patients with type 2 diabetes(T2DM group) and 200 normal controls(NC group),by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method.Chi-square analysis was used to test the genotypes distribution of the two genes followed by Hardy-Weinberg equilibrium.Body mass index(BMI),plasm glucose,serum insulin and lipid profile,HOMA-IR and HOMA-βwere analyzed to estimate the insulin resistance andβ-cell function.Results:①In T2DM group,the frequencies of C allele(χ~2=9.831,P=0.002) and CC genotype of rs13266634 were significantly higher Than those in the NC group (χ~2=12.598,P=0.002)②The C-allele of rs13266634 significantly increased T2DM risk with an allelic odd ratio(OR)of 1.59(OR=1.59,95%CI为1.19-2.11),compared with non-carriers, homozygous carriers of C allele were liable to have type 2 diabetes with OR=2.63(OR=2.63,95%CI=1.42-4.87,χ~2=9.69,P=0.002).③The genotype of CC were associated with decreased insulin secretion but not with insulin resistance.④The genotypes and allele frequencies of TCF7L2(rs11196218) in type 2 diabetes mellitus were not significantly different between cases and controls(P＞0.05). Conclusion:These results indicate that C allele polymorphism of rs13266634 site in SLC30A8 gene might a risk factor for T2DM.Suggesting that SLC30A8 might be a susceptible gene for T2DM in the Southern Chinese Han population,while the polymorphism of rs11196218 site in TCF7L2 gene may not be a risk factor for our Chinese Han population.