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Purpose: To evaluate the possible association of UBASH3B gene rs4936742 (T > C) polymorphism with Behcet's disease (BD) and posterior uveitis in BD. Materials and Methods: One hundred and thirty-one patients with BD (51 Behcet's posterior uveitis and 80 non-ocular Behcet's patients) and 61 unrelated age-matched healthy individuals as a control group without any inflammatory disease were selected. All BD cases were under follow-up and treatment in uveitis or rheumatology clinics for at least 5 years. All research subjects, including control individuals, received a comprehensive rheumatologic evaluation. All patients and controls were genotyped for UBASH3B rs4936742 (T > C) polymorphism by PCR-RFLP technique. Results: The observed frequencies of genotypes were significantly different among patients and controls (19.7% versus 30.5% for TT, OR = 2.9, P = 0.011 and 36.1% versus 45.8% for CT, OR = 2.38, P = 0.017). Frequencies of T allele showed significantly higher values in Behcet's patients (OR = 1.9, P = 0.004). Subgroup genotypic and allelic analyses disclosed no significant difference between Behcet's posterior uveitis and control groups, neither between Behcet's posterior uveitis and non-ocular BD groups. However, genotypic and allelic analyses between non-ocular BD and control groups revealed statistically significant difference (36.3% versus 19.7% for TT, OR = 4.08, P = 0.003 and 43.8% versus 36.1% for CT, OR = 2.68, P = 0.018, 58.1% versus 37.7% for T allele, OR = 2.29, P = 0.001). Individuals carrying the TT genotype for UBASH3B were four times more likely to develop non-ocular BD than unaffected, control individuals. Conclusion: Our results showed that the UBASH3B gene rs4936742 (T > C) polymorphism is associated with an increased risk of Behcet's disease, especially non-ocular BD, in Iranian population. We could not find any susceptibility role of this genetic locus for posterior uveitis in Behcet's disease. [ABSTRACT FROM AUTHOR]

Purpose:To evaluate the possible synergistic effect of at risk genotypes ofARMS2/LOC387715(A69S), DNA repairSMUG1rs3087404,CCL2–2518,C3(R102G),CFH Y402H, complement factor B(L9H), andcomplement factor I(CFI) (G119R) in advanced age-related macular degeneration compared to those of healthy controls. Elucidation of synergistic effects between different genetic loci may clarify their pathogenetic pathways. Methods:We calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) to estimate the additive or supra-additive effects of the mentioned genotypes. Results:ARMS2-CFH [RERI = 4.78 (95% CI 2.17–10.61), AP = 0.65 (95% CI 0.33–0.83), S = 4.11 (95% CI 1.40–12.06)], and CFH-C3 combinations [RERI = 2.71 (95% CI 0.04–7.01) AP = 0.47 (95% CI −0.03–0.7) S = 2.30 (95%CI 0.97–5.45)] have the most significant levels of synergism and C3-CFI combination [RERI = −1.65 (95%CI −4.34–0.06), AP = −0.92(95%CI −3.09 – −0.09), S = 0.32 (95%CI 0.09 = 1.20)] has the most significant level of antagonism. Conclusion:Among different genotype combinations ARMS2-CFH and CFH-C3 combinations have the most significant levels of synergism and C3-CFI combination has the most significant level of antagonism in AMD patients. [ABSTRACT FROM PUBLISHER]

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 ofSMUG1variants 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 regionSMUG1rs3087404. 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 forSMUG1was not different between study groups. No difference ofSMUG1polymorphism 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 andSMUG1genotypes in AMD susceptibility. [ABSTRACT FROM PUBLISHER]

Background: Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population. Inflammatory mediators play an important role in AMD pathogenesis and immune-related gene polymorphisms are shown to increase the risk. Complement system is an important mediator of the immunity system and several genes encoding proteins involved in this system are associated with susceptibility to AMD. The central element of the complement cascade, C3 has been a plausible candidate since its cleavage product C3a was found in drusen. This study was planned to evaluate the association of C3-rs2230199 (R102G) variants with advanced type AMD in this cohort. Materials and methods: In this case-control study, 494 participants consisting of 266 AMD patients (187 wet AMD and 79 advanced dry AMD) and 228 samples from unrelated healthy controls were enrolled for evaluation. Extracted-DNA samples were amplified to obtain fragments including the polymorphic region. Results: The distribution of the R102G genotypes was significantly different in the AMD patients compared to controls (p= 0.001).The Odds Ratio compared to CC individuals was 1.69 (95% CI 1.15–2.49) for GC individuals and 6.48 (95% CI1.87–22.43) for GG individuals. The Odds Ratio compared to the C allele was 2.31 (95% CI 0.48–11) for the G allele. GG and GC genotypes and G allele were significantly associated with both types of advanced-AMD. Individuals carrying GG genotype have over a six-fold risk of developing AMD in comparison to those carrying the CC genotype in this cohort. Our meta-analysis pooled data showed that our homozygous individuals for GG have a higher risk of AMD compared to previous publications in different nations (p= 0.017). Conclusions: Our study shows C3 to be a relatively strong susceptibility gene for advanced-type-AMD (exudative-and-geographic-atrophy) in an Iranian population. [ABSTRACT FROM PUBLISHER]

Purpose To evaluate the association of CC-cytokine ligand 2 CCL2-2518 (rs1024611) single nucleotide polymorphism, complement factor H ( CFH Y402H) and their possible interaction in developing advanced age-related macular degeneration ( AMD). Methods In this case-control study, DNA samples from 266 patients with advanced AMD and 229 healthy controls were genotyped for CCL2 polymorphism and also 254 patients and 164 healthy controls were genotyped for CFH polymorphism. The possible associations of these polymorphisms with susceptibility to AMD independently and in different joint combinations were evaluated. Results The genotype frequency for CFH was found to be significantly different between AMD and normal controls (31.5% versus 20.7%, OR = 3.56, p < 0.001 for CC and 52.4% versus 41.5%, OR = 2.96, p < 0.001 for CT genotype). However, no significant association between CCL2 polymorphism and AMD was observed in this cohort ( OR = 1.15 and OR = 0.8, p = 0.172). Interestingly, studying the joint effects of two genotypes ( TT genotype of CFH Y402H and AG genotype of CCL2-2518) showed more significant protective effect against AMD (p = 0.0001), while the risk effect of CC and CT genotypes of CFH was only visible in the presence of AA genotype of CCL2-2518 (p = 0.044 and p = 0.05). Conclusion Complement factor H Y402H polymorphism is strongly associated with advanced type AMD. Although this study revealed no association of CCL2-2518 with AMD, the risk effect of CFH genotypes was only visible in the presence of AA genotype of CCL2-2518. AG genotype of CCL2-2518 in combination with TT genotype of CFH Y402H showed significant protective effect against AMD. [ABSTRACT FROM AUTHOR]