Abstract
BACKGROUND: Type 1 diabetes (T1D) is a multifactorial autoimmune disease, involving strong genetic components with familial predisposition. Human leukocyte antigen-G (HLA-G) is a non-classical HLA-class I molecule having several immunomodulatory functions. Polymorphisms in HLA-G are associated with several autoimmune diseases including T1D. This study aims to evaluate the association of HLA-G 14bp Ins/Del and +3142 C/G polymorphisms with T1D among the South Indian population. METHODS: The study was performed in a cohort of 123 T1D patients along with their 51 siblings and 126 parents. The association and linkage of HLA-G 14bp Ins/Del and +3142 C/G polymorphisms with T1D were analysed, and transmission disequilibrium test (TDT) was performed. RESULTS: Significantly increased frequencies of HLA-G 14bp Del/Del genotype (OR = 2.16, p(c) = 0.0302) and Del allele (OR = 1.71, p(c) = 0.0398) were observed in female patients compared to parents. Higher frequencies of DelDel/GG combined genotype (OR = 4.45, p(c) = 0.0049) and Del/G haplotype (OR = 2.91, p(c) = 0.0277) were observed in female patients compared to parents. TDT also revealed over-transmission of Del/G haplotype (25T vs 7UT; P = 0.0015) and a strong linkage disequilibrium between the studied polymorphisms. CONCLUSION: This familial study shows the association of HLA-G 3'UTR 14bp Ins/Del polymorphism with the risk of T1D among the South Indian population, especially in females.