The effects of TLR3, TRIF and TRAF3 SNPs and interactions with environmental factors on type 2 diabetes mellitus and vascular complications in a Han Chinese population

• Published in: Gene Vol. 626; pp. 41 - 47
• Main Authors: Zhou, Zixing, Zeng, Chengli, Nie, Lihong, Huang, Shiqi, Guo, Congcong, Xiao, Di, Han, Yajing, Ye, Xiaohong, Ou, Meiling, Huang, Chuican, Ye, Xingguang, Wen, Zihao, Yang, Guang, Jing, Chunxia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.08.2017
• Subjects: Adaptor Proteins, Vesicular Transport - genetics; Aged; alleles; body mass index; Case-Control Studies; China; Chinese people; coronary disease; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetic Angiopathies - genetics; environmental factors; Female; Gene-Environment Interaction; genetic variation; haplotypes; high density lipoprotein; Humans; immunity; inflammation; insulin resistance; interferon-beta; low density lipoprotein; Male; Middle Aged; patients; Polymorphism; Polymorphism, Single Nucleotide; protective effect; risk; signal transduction; single nucleotide polymorphism; T2DM; TLR3; TNF Receptor-Associated Factor 3 - genetics; Toll-like receptor 3; Toll-Like Receptor 3 - genetics; TRAF3; TRIF; T2DM; DPN; IRF-3/7; DN; DR; NF-κB; HDL; SD; UTR; IFN-β; SNP; LDL; HWE; MDR; BMI; DCI; TG; MAF; TRAF3; KCNQ1; TRIF; TLR3; CHD; TLR2; Polymorphism
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2017.05.011

Toll-like receptor 3 (TLR3) is involved in type I interferon-β (IFN-β) via TIR-domain-containing adapter-inducing interferon-β (TRIF) and Tumor necrosis factor receptor–associated factor 3 (TRAF3), culminating in inflammation and immunity reactions. TLR3 is implicated in insulin resistance and type 2 diabetes mellitus (T2DM). Eight SNPs of these genes were detected in 552 T2DM patients and 552 matched healthy control subjects. Gene-gene and gene-environment interactions and haplotype associations were also evaluated. We identified a 21% increased risk of T2DM for the T allele of rs12435483 in the TRAF3 gene (OR: 1.21; 95% CI: 1.01–1.44; P=0.036). The GA genotype and GA+AA genotype of TRAF3 rs12147254 were found to increase the risk of coronary heart disease (CHD) among T2DM patients (GA vs. GG: OR=4.17, 95% CI: 1.04–16.79, P=0.045; GA+AA vs. GG: OR=3.97, 95% CI: 1.02–15.48, P=0.047). However, the GACGAC haplotype in TRAF3 had a protective effect on T2DM micro-macrovascular complications (OR=0.33, 95% CI: 0.13–0.85, P=0.017). Two-factor (TRAF3 rs12435483 and LDL) and three-factor (TRAF3 rs12435483, BMI and HDL) interactions of the risk of T2DM were identified. In conclusion, the genetic variants in the TLR3-TRIF-TRAF3-INF-β signaling pathway and interactions with some particular environmental factors (LDL, BMI and HDL) may contribute to susceptibility to T2DM and vascular complications in the Han Chinese population. •TLR3, TRIF and TRAF3 genes may contribute to susceptibility of T2DM.•Interactions in environmental factor and gene may be associated with T2DM.•Haplotype in TRAF3 gene may protect T2DM vascular complications.