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This case-control study aimed to evaluate the possible association of MCP-1 − 2518A/G genetic polymorphism with Behcet's disease (BD) in the Iranian patients. This study was performed in 135 Behcet's patients (51 ocular and 84 non-ocular) and 79 healthy individuals. Peripheral blood samples were genotyped for MCP-1 − 2518A/G using the PCR-RFLP technique. The statistical analysis of MCP-1 − 2518A/G showed no significant differences in genotype/allele frequencies between Behcet's patients and controls. There was no significant association in genotype/allele frequencies between either ocular or non-ocular BD patients and controls. Also, different genotype/allele frequencies between ocular and non-ocular BD were not statistically significant. In this study, with a threshold P-value of 0.05 and an estimated power of 0.81 to detect a significant association (odds ratio ≥1.2), we did not observe any association of this variant with Behcet's disease. [ABSTRACT FROM AUTHOR]

There are conflicting results of studies investigating the association between the tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) gene polymorphisms and Behcet's disease (BD). The aim of this meta-analysis is to assess the association between these gene polymorphisms and ocular involvement in BD. We identified relevant studies and reviewed the full-text manuscripts of the studies in order to select those for inclusion. Heterogeneity of studies was evaluated using Cochran Q-test and I-square index. To modify the heterogeneity in the variables we used random effects model. Meta-analysis was performed using STATA. We analyzed TNF-1031, −308 and ACE DD/II genotype difference between BD patients with and without uveitis. Among these polymorphic genetic loci TNF-308 AA genotype has a statistically significant protective effect against BD uveitis (OR = 0.45 vs 1.23, p =.017). Such a statistically significant effect was not seen for other studied genotypes. This meta-analysis revealed a significant protective effect of TNF-308 AA genotype against ocular involvement in Behcet's disease. [ABSTRACT FROM AUTHOR]

Abstract: To pool the results of published data regarding association of ARMS2/LOC387715 A69S, CFH Y402H and CFH I62V genotypes with age‐related macular degeneration (AMD) with and without reticular pseudodrusen (RPD). The results of this pooled data used to estimate the contribution of each of these genes in the pathogenesis of RPD. Heterogeneity of studies was evaluated using Cochran Q‐test and I2 index. To modify the heterogeneity in the variables, we used the random effects model. Meta‐analysis was performed using STATA. Odds ratio (OR) of genotypes in each study was calculated. Six studies of AMD with RPD and AMD without RPD cases included in this analysis. Analysis of pooled data showed that risk genotypes frequency of ARMS2 A69S was significantly different between AMD with RPD and AMD without RPD [OR = 1.82, 95% confidence interval (CI): 1.26–2.63 for GT versus GG ARMS2 A69S; OR = 2.40, 95% CI: 1.50–3.84 for TT versus GG ARMS2 A69S]. Further analysis also showed that the risk genotype frequency of CFH Y402H was not significantly different between these two groups (OR = 1.02, 95% CI: 0.69–1.50 for CT versus TT CFH Y402H; OR = 1.09, 95% CI: 0.74–1.60 for CC versus TT CFH Y402H). Comparison of above‐mentioned ORs revealed statistically higher values for GT and TT genotypes of ARMS2 A69S compared with CFH Y402H genotypes (p = 0.011, p = 0.014, respectively).Our analysis showed stronger contribution of ARMS2 in AMD with RPD group versus AMD without RPD group, in comparison with CFH genotypes. [ABSTRACT FROM AUTHOR]

Background: To determine the joint effect of complement component 3(C3 R102G) with CC-cytokine ligand2 (CCL2-2518) or complement factor H (CFH) Y402H polymorphisms on advanced age-related macular degeneration (AMD). Methods: In this case-control study, 233 patients with advanced AMD and 159 unrelated healthy controls enrolled for evaluation. Selected polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Results: A combination of AACCL2(rs1024611) and GG C3 (R102G) genotypes resulted in a super-additivity of the risks: OR = 10.13, 95% CI 1.04–98.49,p= 0.04, adjusted OR = 7.74, 95% CI 0.71–84.75,p< 0.1, adjusted synergy indices: relative excess risk due to interaction (RERI) = 1.38, the attributable proportion due to interaction (AP) = 24.7% and the synergy index (S) = 1.43. Combination of at-risk genotypes ofCFHY402H and C3 R102G resulted in a strong super-additive risk: adjusted OR = 22.65, 95% CI 2.32–220.91,p= 0.007, adjusted AP = 90.4% and the S = 12.86. Attributable proportion of risk owing to C3-CCL2and C3-CFHinteraction calculated at 25% and 90% for advanced AMD. Conclusion: We have previously shown a strong association of C3 (R102G) andCFHY402H with AMD whereas no association was found forCCL2-2518. This study enclosed strong synergistic association of risk genotypes of C3 andCFHY402H with AMD. We also revealed synergistic influence ofCCL2-2518 and the at-risk genotype of the C3 in AMD with an estimated AP = 50.9% (adjusted AP = 24.7%). Present findings show thatCCL2-2518 polymorphism is not an innocent bystander in AMD susceptibility when combined with the at-risk genotype of C3 (R102G). [ABSTRACT FROM AUTHOR]

Purpose: The age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S(rs10490924) polymorphism and cigarette smoking have been shown to have significant association with AMD. In this meta-analysis we used the results of available association studies of combinedARMS2/LOC387715genotypes and cigarette smoking with AMD to estimate the possible synergistic or multiplicative effects. Methods: Heterogeneity of studies was evaluated using the Cochran Q-test and the I-square index. To compensate for the heterogeneity of the variables in the study we used a random effects model. Meta-analysis was performed using STATA. To estimate the additive or supra-additive effects, we calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), synergy index (S), and multiplicative index (V). Results: We could include four studies with 1982 AMD patients and 1797 control subjects. Considering the GG-no smoking as a reference line the meta-analysis result of AMD odds ratios for stratified combined factors was 3.05 (95% CI 2.32–4.02) for nonGG-no smoking, 2.24 (95% CI 1.39–3.63) for GG-smoking and 4.59 (95% CI 3.51–6.01) for nonGG-smoking. The meta-analysis of synergy analysis revealed RERI = 2.01 (95% CI 1.01–3.25), AP = 0.40 (95% CI 0.22–0.54), S = 2.02 (95% CI 1.35–3.01), and V = 1.31 (95% CI 0.94–1.83). Conclusion: This analysis revealed the synergistic effect of these two factors indicating that there is a common pathway ofARMS2/LOC387715and smoking in AMD pathogenesis which may be the complement system pathway. [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: Complement factor H (CFH) Y402H (rs1061170) and age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S (rs10490924) polymorphisms shown to have significant association with age-related macular degeneration (AMD). In this meta-analysis, we pooled the results of the available association studies between combined ARMS2/LOC387715A69S-CFHY402H genotypes and AMD to estimate the possible synergistic or multiplicative effects. Methods: Heterogeneity of studies was evaluated using the Cochran Q-test and the I-square index. To modify the heterogeneity in the variables, we used random effects model. Meta-analysis was performed using STATA. To estimate the additive or supra-additive effects, we calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), synergy index (S), and multiplicative index (V). Results: We included eight studies with 2915 AMD patients and 3505 control subjects. Considering the GGTT genotypes as reference lines, the pooled AMD Odds Ratios for stratified combined genotypes were 2.32 (95% CI 1.64–3.28) for GGnon-TT, 2.49 (95% CI 1.72–3.60) for non-GGTT, and 7.82 (95% CI 5.09–12.00) for non-GGnon-TT. Pooled synergy analysis revealed RERI = 4.08 (95% CI 3.15–5.27), AP = 0.50 (95% CI 0.42–0.57), S = 2.31 (95% CI 1.9–2.82), and V = 1.21 (95% CI 0.93–1.49). Conclusion: This analysis revealed the synergistic and positive multiplicative effect of these two genes indicating that there is a common pathway of ARMS2/LOC387715 and CFH in AMD pathogenesis which may be the complement system pathway. [ABSTRACT FROM AUTHOR]

Purpose: Age-related macular degeneration (AMD) as the leading cause of central visual loss in the developed countries has extensive pathologic similarities with Alzheimer's disease (AD). Saitohin rs62063857 Q7 R polymorphism is associated with increased risk of AD though we decided to evaluate the possible association of this polymorphism with advanced AMD. Materials and Methods: 152 advanced AMD patients (134 wet AMD and 18 geographic atrophy) and 75 healthy controls included in this study. Cases and controls went through a standard ophthalmologic examination by a retinal specialist. Saitohin gene rs62063857 polymorphism determined by using PCR technique and restriction enzyme HinFI. To evaluate the differences between groups we used t-test, Chi-Squared and one-tailed Fisher exact test. Results: Distribution of genotypes was not significantly different between total AMD or wet AMD patients compared to that of controls (total AMD RR+QR: OR = 1.51, CI = 0.82–2.79, P =.12; wet AMD RR+QR: OR = 1.39, CI = 0.74–2.59, P =.19). The RR+QR genotypes were significantly higher in dry AMD group compared to that of controls (RR+QR: OR = 2.75, CI = 0.96–7.9, P =.05). Conclusion: Our results showed that although STH Q7 R polymorphism was not associated with wet AMD susceptibility it was significantly associated with geographic atrophy. [ABSTRACT FROM AUTHOR]