title: Association of polymorphisms in the MyD88, IRAK4 and TRAF6 genes and susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a southern Han Chinese population.
abstract: Type 2 diabetes mellitus (T2DM) has been linked to a state of low-grade inflammation resulting from abnormalities in the innate immune pathway. MyD88 is an essential adaptor protein for TLR signaling, which is involved in activating NF-κB through IRAK4 and TRAF6. To investigate the effects of the MyD88, IRAK4 and TRAF6 polymorphisms in the susceptibility of T2DM and diabetic vascular complications, eight SNPs were analyzed in 553 T2DM patients and 553 matched healthy controls. Gene-gene interactions and haplotype associations were also evaluated. We found a significant increased risk of T2DM for the AG genotype of rs6853 in MyD88 gene and the CT genotype of rs4251532 in IRAK4 gene. Significant association was also found between rs16928973 in TRAF6 gene and diabetic nephropathy (DN) under the allelic model. Moreover, the TA haplotype in TRAF6 was negatively associated with DN. No significant gene-gene interactions were found. In conclusion, our results indicate that the polymorphisms in TLR-MyD88-NF-κB signaling pathway confer genetic susceptibility to T2DM and DN.
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Liju
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Endocrine, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Nie
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Di
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Ou
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Baohuan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Medical Statistics, School of Medicine, Jinan University, Guangzhou 510632, China.
authors.forename: Hansheng
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Parasitology, School of Medicine, Jinan University, Guangzhou 510632, China; Key Laboratory of Environmental Exposure and Health in Guangzhou, Jinan University, Guangzhou 510632, China. Electronic address: guangyangphd@gmail.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, 510632, China; Key Laboratory of Environmental Exposure and Health in Guangzhou, Jinan University, Guangzhou 510632, China. Electronic address: jcxphd@gmail.com.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Jing
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D004843:Epistasis, Genetic; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics*
chemical_list: D053594:Myeloid Differentiation Factor 88; D048029:TNF Receptor-Associated Factor 6; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: Genetics; IRAK4; MyD88; T2DM; TRAF6