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 (N = 219 controls and 90 XFS cases) from India. PCR based direct sequencing was performed for candidate genes (LOXL1, POMP and TMEM136) 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 (LOXL1) and rs3737528 (POMP) showed significant association with XFS. LOXL1 gene haplotype GAGC (rs1048661- rs3825942- rs41435250-rs8818) was associated with lower risk for XFS with a p value 4.1961 × 10-6 (OR =0; 95%CI, 0.000-0.003). POMP 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 LOXL1 (ρ= -0.132) and rs3737528 of POMP (ρ = 0.12) was observed with measure of lifetime UV exposure (CUVAF value). Reduced LOXL1 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 LOXL1 promoter region. CONCLUSION: Our results suggest a possible interaction for LOXL1 gene haplotype (GAGC) with the measure of ocular UV exposure in pseudoexfoliation syndrome.

Evaluating the impact of ocular UV exposure for the development for pseudoexfoliation syndrome in a South Indian population.

CLINICAL RELEVANCE: Pathophysiology of pseudoexfoliation syndrome (XFS) can be influenced by environmental factors such as solar exposure/occupational factors and genetic factors. BACKGROUND: The study aims to assess the association of lifetime ocular UV exposure and its impact on the risk of development of XFS. METHODS: All eligible subjects underwent a comprehensive ocular examination. XFS was defined as precipitates on the pupillary border, cornea, and angle of anterior chamber or lens in at least one eye without any clinical signs of glaucoma. A standardised questionnaire was administered to assess the lifetime UV exposure. Conjunctival ultraviolet autofluorescence (CUVAF) photography was taken to detect the conjunctival changes with exposure to UV radiation. Ascorbic acid concentration in the aqueous humour was measured. RESULTS: A total of 404 subjects of which 274 (controls) and 130 (XFS cases) were studied. There were 204 males (50.5%) and 200 females (49.5%).Lifetime UV exposure (OR: 1.14, 95% CI: 1.02-1.30, p: 0.032), CUVAF damage (OR: 1.03, 95% CI: 1.01-1.06, p: 0.008) and outdoor worker (OR: 1.87, 95% CI: 1.18-3.00, p: 0.008) were positively associated with XFS. Usage of spectacles (OR: 0.63, 95% CI: 0.39-0.95, p: 0.030) and ascorbic acid concentration in aqueous (OR: 0.47, 95% CI: 0.23-0.99, p: 0.038) were found to be protective against XFS. CONCLUSION: Besides genetic factors, environmental factors such as lifetime ocular UV exposure and outdoor work are significantly associated with the risk of XFS. CUVAF can be used as a non-invasive tool to detect preclinical sun damage in outdoor workers.