CTLA 4+49G allele associates with early onset of type 1 diabetes in North Indians

Summary Type 1 diabetes (T1D) is a complex autoimmune disease with strong genetic influence. In this study, we investigated +49A/G SNP (rs 231775) in exon 1 of cytotoxic T‐lymphocyte‐associated antigen 4 ( CTLA 4) by PCR ‐ RFLP and its influence as a risk factor for the disease in the North Indian population. This polymorphism at codon 17 results in an amino acid substitution (Thr/Ala) in the leader peptide of the molecule. The study included 232 patients with T1D (age at onset of disease ( AOD ): 0.5–37 years) and 305 ethnically matched healthy controls. The DNA obtained from these 537 individuals was amplified using a set of specific primers followed by restriction enzyme digestion with Fnu4 HI . The +49G allele as well as its homozygous genotype G/G was observed to be significantly higher in patients as compared to the healthy controls {(37.3% vs. 25.6%, P  =   4.96E −05 , OR  = 1.73; 95% CI  = 1.33–2.25) (15.52% vs. 6.6%, P  =   0.001, OR  = 2.62; 95% CI  = 1.48–4.63) respectively}. The frequency of G/G genotype was significantly higher in patients with early age at onset of disease ( AOD :<12 years) as compared to that in the late‐onset patients with AOD : ≥12 years (21.1% vs. 10.6%, P  =   0.042, OR  = 2.26; 95% CI  = 1.09–4.67) as well as to that in the healthy controls (21.1% vs. 6.6%, P  =   0.00004, OR  = 3.8; 95% CI  = 2.01–7.2). Further analysis revealed that the median AOD significantly reduced ( P  =   0.049) from 14 years in patients with A/A genotype to 11 and 10 years in those with A/G and G/G genotypes, respectively. These results suggest that CTLA 4+49G allele, particularly in homozygous G/G condition, associates with early onset of T1D.