Association Between Polymorphisms In Toll-like Receptor4Signaling Pathways Gene And Type2Diabetes Mellitus

ObjectiveType2diabetes was closely associated with immune and inflammation. It is one of asignificant health problem worldwide. However, the pathogenesis of T2DM has not yet beenfully elucidated. Toll like receptor4was considered an important receptor that plays a key rolein development of insulin resistance and complication. Animal experiments showed thatactivation of TLR4and downstream cytokine production lead to the development of diabetes.But it is still unknown whether this signaling pathways genetic variation is associated withT2DM. The aim of this study was to investigate whether the polymorphisms in TLR4, MyD88,IRAK4and TRAF6gene are associated with T2DM.Methods1. This was a matching case-control study. A total of1106subjects were included in thestudy. The population included553subjects with T2DM and553control subjects. GenomicDNA was extracted from peripheral whole blood samples.2. All clinical information was collected in cases and controls.3. All Single nucleotide polymorphisms (SNPs) in the TLR4, MyD88, IRAK4and TRAF6gene on human chromosomes were from the human genome database. Preliminary experimentsto determine the SNPs in TLR4, MyD88, IRAK4and TRAF6genes. All SNP genotyping usingthe Sequenom MassARRAY iPLEX platform.4. Associations between the analyzed the polymorphisms which in TLR4, MyD88, IRAK4,TRAF6gene and T2DM were evaluated. All of the statistical analyses were performed withStatistical Product and Service Solutions software13.0.Results1. Selected a total of15SNPs in the four genes, including TLR4gene (rs1927914,rs1927911, rs1927907, rs2149356, rs11536889, rs7873784and rs1927906), MyD88gene(rs7744, rs6853), IRAK4gene (rs4251569, rs1461567, rs42515113, rs4251532) and TRAF6gene (rs16928973, rs5030445).2. There were significant differences between cases and controls in body mass index, low density lipoprotein, high density lipoprotein and triglycerides. The P-value was less than0.05.There were no significant differences between cases and controls in total cholesterol.3. Using matching case-control study, after adjusting the BMI, LDL, HDL and TG, therewere no significant association between T2DM and the single nucleotide polymorphisms inTLR4and TRAF6gene. There were significant associations between rs6853in MyD88gene andrs4251532in IRAK4with T2DM risk.4. There were no significant differences in TLR4, MyD88, IRAK4and TRAF6geneshaplotypes between T2DM patients and control subjects.ConclusionsOur results indicate that MyD88and IRAK4genes may be associated with geneticsusceptibility of type2diabetes.