TIM-3 polymorphisms in type 1 diabetes families.

TIM-3 is a transmembrane protein preferentially expressed on differentiated Th1 cells, which play a role in Th1-mediated diseases including type 1 diabetes. We investigated the role of the rs10515746 (A/C), rs1036199 (A/C), and rs10053538 (A/C) single nucleotide polymorphisms (SNPs) within the TIM-3 gene in 186 German type 1 diabetes families (558 individuals) and its interaction with human leukocyte antigen (HLA) high-risk haplotypes DQ2(DQA*0501-DQB*0201)-DQ8 (DQA*0301-DQB*0302). Alleles A, C, and A of the rs10515746 (A/C), rs1036199 (A/C), and rs10053538 (A/C) SNPs were found in a frequency of 20.4%, 19.0%, and 4.2%, respectively. Transmission analysis of these polymorphisms did not show any significant difference. Although in patients with HLA DQx/x (neither HLA DQ2 nor DQ8) an undertransmission of allele A (14.3% vs. 85.7%) of the rs10053538 (A/C) SNP and an overtransmission of allele A (66.7% vs. 33.3%) of the rs10515746 (A/C) SNP was observed, these associations did not remain statistically significant after correction for multiple comparisons. Although we found no association of TIM-3 with type 1 diabetes in the German population, we cannot discard a possible association in a larger size.