Objective: To investigate whether a single nucleotide polymorphism (SNP) rs1136410 in the poly (ADP-ribose) polymerase-1 (PARP-1) gene was associated with PARP activities, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, and the risk of age-related cataract (ARC) in a Chinese Han population.
Methods: In this two-stage case-control study with a total of 1010 ARC patients and 1045 controls, SNP rs1136410 was genotyped by high-resolution melting analyses (HRM). PARP activities and 8-OHdG levels in peripheral blood mononuclear cells (PBMCs) were determined by ELISA kits.
Results: In discovery, replication, and their merged sets, the variant genotypes (AG+GG) of SNP rs1136410 were significantly associated with an increased risk of ARC under a dominant model (Adjusted odds ratio (OR)=1.42, Padj=0.001 for the merged set). This association was further identified in subtype analyses for cortical ARC (Adjusted OR=1.69, Padj<0.001). In subgroup analyses, we identified a significant interaction between SNP rs1136410 and smoking habit in increasing ARC risk (Pinter=0.019). Moreover, ARC patients had lower activities of PARP and higher levels of 8-OHdG than controls. There were significant correlations of SNP rs1136410 with decreased PARP activities and increased 8-OHdG levels in controls and patients with cortical ARC.
Conclusions: This study suggests that SNP rs1136410 may confer susceptibility to ARC by affecting PARP activities and oxidative DNA damage.
Keywords: Age-related cataract; Oxidative DNA damage; PARP activity; rs1136410.
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