The Association Study Of TCF7L2,AKT2,FOXO1 Gene Polymorphisms With Type 2 Diabetes In Tianjin Han Population And Families

Objective:WNT signaling pathway can affect the development of the pancreas cells and regulate 13-cells'function, including insulin secretion, cell survival, proliferation and so on. The protein which is encoded by transcription factor 7 like 2 (TCF7L2) gene is a key factor of the WNT signaling pathway and it can regulate theβcell functions.It is five times with the gene mutation developing to type 2 diabetes than the normal. Forkhead transcription factor-1 (FOXO1) and TCF7L2 competitive theβ-catenin (β-cat), the FOXO1 gene mutations can impact of its downstream target gene expression, then increased hepatic glucose output and declinedβcells functions. Serine/threonine protein kinase B (AKT2) which was mainly expressed in insulin sensitive tissues, can phorsphorylate the FOXO1. AKT2 gene mutations may be associated with insulin resistance, hyperlipidemia and T2DM. Our study is to analysis the TCF7L2, AKT2,FOXO1 gene polymorphisms and T2DM relationship among T2DM group, the family group and the case control group in Chinese Han population in Tianjin.Methods:Using the fasting blood samples for extracting the genome DNA, then use the denaturing high performance liquid chromatography to detect the PCR amplified fragments, and choose the different peaks for sequencing. The SPSS 13.0 statistical software was used for analysising the clinical data and genotype frequencies.Results:①The TCF7L2 gene G/T genotype frequencies were 18.5% and 2.8% in the T2DM group and NC group, there were statistically differences between the two groups (P<0.05). The levels of HOMA-βwere significantly different between the G/G,G/T genotype subgroups in T2DM group (P<0.05), the frequencies of rs12255372 G/T genotype in diabetic nephropathy and coronary complications have no differences (P>0.05), TCF7L2 gene rs12255372 G/T genotype and allele frequencies in PT2DM group,PDR group and among different glucose tolerance groups were no significant differences, while the differences in FIGT group and the NC group were significant (P<0.05).②In T2DM and NC groups no T/T genotype of rs11669332 site were detected, C/T genotype frequencies in the two groups were 7.7% and 3.4%, T allele frequencies were 3.8% and 1.7%, the differences were not statistically significant (P>0.05).③There were significantly differences in rs2701891 T/C, C/C genotype of FOXO1 gene in T2DM group and NC group, the populations carrying T/C, C/C variances can exist obviouslyβ-cell dysfunction in low level of BMI and fasting glucose. The frequencies of rs2701891 T/C,C/C genotype in diabetic nephropathy and coronary complications have no differences(P>0.05), rs2701891 genotype and allele frequencies between PT2DM group and PDR group, and among different glucose tolerance groups were no significant differences too(P>0.05).④To analysis TCF7L2 and FOXO1 joint genotype frequencies, the T allele of TCF7L2 and the C allele of FOXO1 was statistically significant difference within the NC and T2DM groups, and there were no differences in different glucose tolerance groups⑤ogistic regression analysis showed that the TCF7L2 gene rs12255372 G/T genotype, FOXO1 gene rs2701891 T/C, C/C variances, HbAlc, BUN, HOMA-IR are the risk factors of T2DM. HDL, INSO, IAI, HOMA-βare protective factors. FOXO1 gene T/C, C/C genotype are the risk factors of familial aggregation of T2DM.Conclution:①CF7L2 gene rs 12255372 G/T genotype may be associated with T2DM in Tianjin Han population, but it was not related to the nephropathy and coronary complications in T2DM. The G/T genotype of rs12255372 were higher in FIGT group than the others, suggesting that the G/T genotype may affect the isletβcell functions in T2DM patients, but the mechanisms need further investigation.②There were no relation between the AKT2 gene rs 11669332 site and T2DM in Tianjin Han population.③FOXO1 gene rs2701891 T/C, C/C genotype may be associated with the T2DM, but not related to the nephropathy and coronary complications of T2DM. FOXO1 gene rs2701891 T/C, C/C genotype were not the key risk factors of T2DM among family subgroups.④In the T2DM group and family populations, the variances inTCF7L2 gene and the FOXO1 gene may have no synergy, but the Logistic regression showed that:the two SNPs inTCF7L2 gene and FOXO1 gene were risk factors of T2DM.