Polymorphisms of the gamma crystallin A and B genes among Indian patients with pediatric cataract

Background: Previous familial studies have reported co-segregation of mutation in gamma crystallin A and B CRYGA and CRYGB genes with childhood cataract. Aim: We investigated association of nucleotide variations in these genes in subjects with and without pediatric cataract from India. Settings and Design: The study included 195 pediatric subjects including healthy children with no ocular defects and pediatric cataract cases. Materials and Methods: Subjects were genotyped by PCR-RFLP method for exonic and intronic genetic variations in CRYGA and CRYGB. Statistical Analysis: The association of these polymorphisms with cataract was estimated by two way contingency tables and the risk allele was also analyzed for their functional impact using in silico tools. Results: No significant difference was observed between cases and control subjects for the frequencies of SNPs G198A (Intron A), T196C (Exon 3) of CRYGA and G449T (Exon 2) of CRYGB gene. −47C allele of rs2289917 in CRYGB showed the strongest association with cataract (Odd Ratio-OR=3.34, 95% Confidence Interval-CI 95% =1.82-6.12, P =0.00007). In silico analyses revealed that this polymorphism lies in a phylogenetically conserved region and impacts binding of a transcription factor, viz. progesterone receptor (PR) to CRYGB promoter. Conclusion: rs2289917 risk allele showed a strong association with increased vulnerability for pediatric cataract. The findings suggest that this association may be a secondary phenomenon related to genetic variation playing critical role in lens development during perinatal and/or pediatric growth. Present exploratory study provides a basis for further defining the role of PR as a regulator of CRYG locus in lens formation/transparency.