CTLA-4 gene polymorphism at position +49 A>G in exon 1: a risk factor for cervical cancer in Indian women.

Single nucleotide polymorphisms (SNPs) in the CTLA-4 gene exert differential effects on T-cell response to viral infection. We aimed to evaluate the association of two SNPs of the CTLA-4 gene with cervical cancer in Indian women. The two polymorphic loci, one in the promoter region -318 C>T, rs5742909 (100 cervical cancer cases and 101 controls) and the other in exon 1 +49 A>G, rs231775 (104 cervical cancer cases and 162 controls) were genotyped using polymerase chain reaction-restriction fragment length polymorphism methods. Haplotype block structure was determined using Haploview 4.2. The statistical analyses were performed using a commercially available statistical software package, whereas PyPop was used to calculate the haplotypic frequencies. In this case-control study, the A/A genotype frequency (30.76% vs. 17.6%, P = 0.01) as well as the allelic frequency for A (52.8% vs. 43.5%, P = 0.04) was significantly higher in cases compared to controls. No significant association was seen in the -318 C>T polymorphism. In forward stepwise binary logistic regression analysis considering age and parity as potential confounders, significant association was demonstrated between +49 A/A and cervical cancer. Most likely, this is the first study from India to highlight the significant association between the CTLA-4 gene +49 A/A SNP and cervical cancer, thus adding to the global knowledge of the association of this SNP with cervical cancer.