Association of the DNA repair SMUG1 rs3087404 polymorphism and its interaction with high sensitivity C-reactive protein for age-related macular degeneration in Iranian patients

Background: Age-related macular degeneration (AMD) is a complex disease and recently the role of DNA repairing genes in its susceptibility has been studied. It has been hypothesized that polymorphism in DNA repair system genes reduce the capacity to repair DNA damages which may lead to a greater susceptibility to AMD. C-reactive protein (CRP) production is shown to enhance inflammatory processes by increasing oxidative stress and inducing DNA damage. We planned to evaluate the possible association of SMUG1 variants and their possible interaction with high sensitivity CRP levels in AMD.

Materials and methods: We included 500 case-control samples consisting of 279 advanced type AMD patients and 221 genetically unrelated healthy controls enrolled for evaluation. Extracted-DNA samples were amplified to obtain fragments including the polymorphic region SMUG1 rs3087404. We calculated relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) to clarify possible interaction of different genotypes and CRP levels for AMD.

Results: The distribution of the genotypes were not significantly different in the AMD patients compared to that of controls (p = 0.849). The allele frequency for SMUG1 was not different between study groups. No difference of SMUG1 polymorphism between case and control groups was evident in higher CRP levels (CRP>3mg/dl) compared with lower CRP levels. SMUG1/CRP synergy indices calculated as RERI = ?0.12 and AP = ?0.18 while S was not calculable.

Conclusions: Our study showed that c.-31A/G-SMUG1 genotypes/alleles do not have any association with the occurrence or severity of advanced type AMD. There was no interaction of CRP levels and SMUG1 genotypes in AMD susceptibility.