TIM-3 polymorphisms in type 1 diabetes families

Abstract

Abstract

T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status

“…TIM3 is suspected to protect from T-cell-mediated autoimmune diseases, but many studies on TIM3 polymorphisms reported inconclusive results. However, a small number of studies have indicated significant associations between TIM3 polymorphisms and atopic disease [13,14], whereas other studies on various T-cell-mediated autoimmune diseases, including atopic dermatitis, asthma, type 1 DM, and ITP, have failed to demonstrate an association [15][16][17][18][19]. In a study conducted by Brü ck et al, no direct association was reported between TIM3 polymorphisms and type 1 DM, but a protective trend was reported for the rs10053538 TIM3 polymorphism, especially in patients without HLA-DQ2 or ϪDQ8 (genetic risk factor for type 1 DM) [18].…”

“…Haplotype analysis also failed to demonstrate Bonferroni correction of p value by multiplying with 6 SNP analysis. significance in a type 1 DM study [18]. In a study conducted by Wu et al, no significant association was reported between TIM3 SNP and asthma, but the haplotype GGG (composed of the TIM3 SNPs rs10053538, rs13170556, and rs9313441) was reported to be negatively associated with asthma [17].…”

“…The rs35960726 TIM3 polymorphisms may be an independent risk factor for RA because RA-susceptible HLA (SE) and TIM3 are located on different chromosomes (chromosomes 6 and 5, respectively), and the risk contribution made by SE to RA susceptibility was excluded by our analysis of RA patients without SE. A similar method was used for TIM3 SNP analysis for type 1 DM without susceptible HLA [18]. In the haplotype analysis conducted in the present study, CCAA was determined to be protective, but CCGA, CCGC, and CAAA were determined to be associated with RA development.…”

“…Furthermore, TIM3 pathway activation is believed to inhibit aggressive Th1-mediated auto-and alloimmune responses [11]. Such findings indicate an immune regulatory effect and, thus, TIM3 polymorphisms studies have been conducted in various autoimmune diseases, such as rheumatoid arthritis (RA), atopic disease (atopic dermatitis, asthma), type 1 diabetes mellitus (DM), and immune thrombocytopenic purpura (ITP) [12][13][14][15][16][17][18][19].…”

“…The rs10515746 (promoter at position Ϫ574) and rs1036199 (exon 3 at position 4259) single nucleotide polymorphisms (SNPs) have been evaluated in RA by Chae et al [12] as well as in type 1 DM and ITP [18,19], but no significant associations were reported. Three other SNPs in the TIM3 gene, namely, rs4704846 (3= untranslated region A/G, reported in an atopic disease study by Page et al [15]) and rs11742259 (intron at position Ϫ5939 C/T) and rs11134551 (intron at position 30762 A/G; both reported in an asthma study by Gao et al [16]), have been reported not to be significantly associated with atopy or asthma, respectively.…”