Abstract
PURPOSE: Introns play an important role in gene regulation and expression. Single nucleotide polymorphisms (SNPs) in introns have the potential to cause disease and alter the genotype-phenotype association. Hence, this study aimed to decipher the association of SNPs in the introns of the crystallin gene in congenital cataracts. METHODS: SNPs in the introns of crystallin gene family - CRYAA (rs3788059), CRYAB (rs2070894), CRYBA4 (rs2071861), and CRYBB2 (rs5752083, rs5996863) - were genotyped in 248 participants consisting of 141 congenital cataracts and 107 healthy controls by allele-specific oligonucleotide polymerase chain reaction method. Around 10% of samples for each SNPs were sequenced to confirm the genotypes. The allele, genotype, and haplotype frequency were evaluated by the SHEsis online tool. RESULTS: Using dominant model, the "A" allele of rs3788059 was found to have an increased risk toward congenital cataract development whereas the "G" allele was found to be protective (AA + AG vs. GG; odds ratio [OR] 95% confidence interval [CI] = 3.73 [1.71, 8.15], P = 0.0009). The "A" allele of both rs2070894 (AA + AG vs. GG; OR [95% CI] = 0.49 [0.29, 0.84], P = 0.012) and rs5752083 (AA + AC vs. CC; OR [95% CI] = 0.25 [0.08, 0.76], P = 0.016) were suggested to have a protective role by the dominant model. The A-C-T haplotype (rs2071861, rs5752083, and rs5996863) was found to be a significant risk factor for the development of congenital cataract. CONCLUSION: Intronic SNPs in crystallin genes may play a role in the predisposition toward congenital cataract. However, the present findings need to be replicated in a large cohort with more number of samples.