Association of the polymorphism for Toll-like receptor 2 with type 1 diabetes susceptibility.
Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease in which pancreatic beta cells are selectively destroyed. Although autoimmune diseases are driven by inappropriate adaptive immunity, innate immunity may play a role in the development of T1DM. We investigated the association of the genes for toll-like receptor 2 (TLR2), one of the key surface receptors on innate effectors, with T1DM in Korean patients. Genetic association analyses revealed that the genotype composed of the rare allele (CC) of TLR2 1350 showed weak and protective association with T1DM (OR = 1.7, 95% CI: 1.1-2.7; P < .05) irrespective of the duration of disease, age, and autoantibody status. One of the TLR2 SNP haplotypes, TLR2-Ht4, was strongly associated with T1DM in that those subjects having more than one copy of Ht4 showed strong protection from developing T1DM (OR = 90.5; 95% CI: 13.8-235.7; P < 10(-5)). The TLR2 polymorphisms are associated with T1DM, and distribution differences between T1DM versus controls were not influenced by the HLA genes. There is a close relationship between innate and adaptive immunity.
Park
Yongsoo
Y
Dept. of Internal Medicine, Hanyang University Hospital, 249-1 Kyomun-dong, Kuri, Kyunggi-do, Korea 471-020. parkys@hanyang.ac.kr
Park
Sukyung
S
Yoo
Eunkyung
E
Kim
Dukhee
D
Shin
Hyongdoo
H
D000328:Adult; D000483:Alleles; D044466:Asian People; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D016022:Case-Control Studies; D002675:Child, Preschool; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000032:analysis / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D007723:Korea; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface / Q000235:genetics*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D001323:Autoantibodies; C096322:ICA512 autoantibody; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D005968:Glutamate Decarboxylase