A Study on the Candidate Gene Association and Interaction with Measures of UV Exposure in Pseudoexfoliation Patients from India.

PURPOSE

Environmental and genetic factors are associated with development of Pseudoexfoliation syndrome (XFS). Here we intended to elucidate the association of candidate genes in relevance to UV exposure in these patients.

METHODS

This is a case-control study of 309 subjects ( = 219 controls and 90 XFS cases) from India. PCR based direct sequencing was performed for candidate genes ( and ) followed by genotype and haplotype analysis. The promoter methylation status was assessed by Methylation specific PCR based direct sequencing of genomic DNA for all samples. The methylation status was compared with that of primary fibroblasts cultures established from patient's Tenon's tissue samples in subset of these patients.

RESULTS

SNPs rs3825942, rs41435250, rs8818 () and rs3737528 () showed significant association with XFS. gene haplotype GAGC (rs1048661- rs3825942- rs41435250-rs8818) was associated with lower risk for XFS with a p value 4.1961 × 10 (OR =0; 95%CI, 0.000-0.003). gene haplotypes for intronic SNPs (rs1340815- rs3737528- rs913797) TCC and TTC were associated with increased risk for the disease (OR > 1.0). Significant correlation for SNPs rs3825942 of (ρ= -0.132) and rs3737528 of (ρ = 0.12) was observed with measure of lifetime UV exposure (CUVAF value). Reduced gene expression was observed in cultured tenon fibroblasts from the patients that correlated with differential methylation of the Sp-1 binding sites at -253, -243bp upstream to the transcription start site of promoter region.

CONCLUSION

Our results suggest a possible interaction for gene haplotype (GAGC) with the measure of ocular UV exposure in pseudoexfoliation syndrome.