Promoter region ‐318 C/ T and ‐1661 A/G CTLA‐4 single nucleotide polymorphisms and type 1 diabetes in North Indians

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Abstract
Single nucleotide polymorphisms (SNPs) of the CTLA‐4 gene have been associated with manifestation of type 1 diabetes in several populations. We assessed the association of five SNPs present in the CTLA‐4 gene [‐318C/T, ‐1661A/G and ‐1722C/T in the promoter region, +49A/G in exon 1 and CT60 in the 3′ untranslated region (UTR) region] with type 1 diabetes in North Indian subjects. Genotyping was performed in the patients (n = 130) and the healthy control (n = 180) subjects by polymerase chain reaction‐fragment length polymorphism analysis using MseI, BbvI, BstEII and NcoI restriction endonucleases for the ‐318, ‐1661, ‐1722, +49 and CT60 SNPs, respectively. The frequency of G alleles at ‐1661 locus was significantly higher in the patient group compared with the control subjects. Although the frequency of T alleles at ‐318 SNP was significantly higher in patients with type 1 diabetes compared with the controls, it did not remain significant after Bonferroni correction for the number of alleles tested. The frequencies of C/T alleles and genotypes at ‐1722C/T and G allele at +49A/G and CT60 SNPs were not significantly different between the patient and the control groups. Of the various possible haplotypes constructed using the five genetic loci tested (‐318, ‐1661, ‐1722, +49, CT60), the frequency of ‘TGTAG’ haplotype was significantly higher in the patients when compared with the controls. The results of the present study indicate that the presence of G allele at ‐1661 locus at the CTLA‐4 gene (IDDM12 locus) is associated with increased susceptibility to type 1 diabetes in North Indians, whereas A allele is protective.