Association between complement factor I gene polymorphisms and the risk of age-related macular degeneration: a Meta-analysis of literature.
ABSTRACT: AIM:To systematically review the association between complement factors I (CFI) polymorphisms and age-related macular degeneration (AMD) and to explore whether CFI polymorphisms are associated with AMD. METHODS:Meta-analysis of articles published from 1995 to January 2015 of articles involved with AMD and polymorphisms of the CFI gene. Eligible data were pooled in a Meta-analysis, analyzing using STATA software (version 12.0), Review Manager (version 5.2) and different models based on the heterogeneity of effect sizes. Egger's test, Begg's rank correlation methods were used to evaluate for publication bias. RESULTS:Thirteen articles were eligible, describing two loci polymorphisms of the CFI gene (of which 12 articles focus on rs10033900T>C and 3 articles focus on rs2285714C>T). For rs10033900T>C, the results of our study revealed that having a mutant allele C, TC, CC and TC+CC was associated with a decreased risk of AMD in all population groups studied (C versus T models, OR=0.84, 95%CI: 0.72-0.99, P=0.04; TC versus TT models OR=0.89, 95%CI: 0.88-0.99, P=0.04; CC versus TT models, OR=0.76, 95%CI: 0.60-0.98, P=0.03; TC+CC versus TT models, OR=0.81, 95%CI:0.65-0.99, P=0.04). We found that C allele were related to lower AMD risk in the Caucasian population by subgroup analysis, but there was no association with AMD under the allele and genotypes comparison in Asian studies. For rs2285714 C>T, the TC, TT genotypes contributed to a higher risk of AMD, compared with the CC carriers and TC+CC (OR=1.34, 95%CI: 1.09-1.63, P=0.004; OR=1.50, 95%CI: 1.25-1.80, P<0.0001). CONCLUSION:This Meta-analysis suggests that CFI rs10033900T>C and rs2285714C>T polymorphisms may contribute to AMD.
Project description:Associations between vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, and rs3025039) and risk of age-related macular degeneration (AMD) have been extensively studied, but the currently available results are contentious rather than conclusive. Therefore, we performed the present meta-analysis to further assess the associations. Literature search in PubMed, Embase, and Web of Science databases was conducted until April 2013. The strength of the associations between VEGF polymorphisms and AMD risk was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Both models of fixed effects and random effects were performed to summarize the pooled ORs. All data were analyzed by Stata software 12.0. The meta-analysis results based on nine case-control studies with 2427 cases and 2037 controls showed that rs833061 had protective effects on AMD risk (TT vs. CT+CC: OR=0.58, 95% CI=0.41-0.81), whereas rs1413711 (TT vs. CT+CC: OR=1.46, 95% CI=1.10-1.93) and rs3025039 (TT vs. CC: OR=1.87, 95% CI=1.15-3.02; TT vs. CT+CC: OR=2.09, 95% CI=1.30-3.37) represented as risk factors for AMD. Subgroup analysis by ethnicity suggested significantly reduced risk in Caucasians (TT vs. CT+CC: OR=0.60, 95% CI=0.36-0.99; T vs. C: OR=0.89, 95% CI=0.78-1.00) and Asians (TT+CT vs. CC: OR=0.57, 95% CI=0.34-0.96; TT vs. CT+CC: OR=0.54, 95% CI=0.33-0.90) for rs833061, yet elevated risk in Caucasians (TT vs. CT+CC: OR=2.05, 95% CI=1.24-3.38) for rs1413711 and in Asians (TT vs. CC: OR=2.06, 95% CI=1.24-3.43; TT vs. CC: OR=2.34, 95% CI=1.42-3.89) for rs3025039. In stratified analysis by type of AMD, rs833061 was observed to decrease wet AMD risk, while rs1413711 and rs3025039 were found to increase the risk of wet AMD. Based on the currently available data, this meta-analysis suggests that the VEGF polymorphisms may be associated with risk of AMD, particularly wet AMD.
Project description:The effects of the programed cell death 1 (PDCD1) gene polymorphisms on cancer risk have been investigated in some studies; however, the results were conflicting and ambiguous. Therefore, we aimed to do a meta-analysis to investigate the association of PDCD1 polymorphisms with cancer risk from all eligible case-control studies.An electronic search of the PubMed, Embase, Chinese National Knowledge Infrastructure, and Wanfang databases was performed. The association between PDCD1 polymorphisms with cancer risk was calculated with odds ratios (ORs) and their corresponding 95% of confidence intervals (CIs).A total of 24 case-control studies from 13 articles that investigated the associations of 5 widely studied polymorphisms in PDCD1 gene and cancer risks were included. The results of meta-analysis: the PDCD-1.5 (rs2227981) and PDCD-1.3 (rs11568821) polymorphisms were associated with decreased risk of cancer (rs2227981: OR = 0.75, 95% CI: 0.64-0.86, P < 0.0001 for TT vs TC + CC; rs11568821: OR = 0.79, 95% CI: 0.65-0.96, P = 0.02 for TC vs TT), while no significant associations were found for the other 3 polymorphisms (PDCD-1.9 [rs2227982] polymorphism: OR = 1.03, 95% CI: 0.90-1.18, P = 0.66 for CC + TC vs TT; PDCD1 rs7421861 polymorphism: OR = 1.10, 95% CI: 0.96-1.25, P = 0.16 for CC + TC vs TT; PDCD-1.6 [rs10204525] polymorphism: OR = 0.93, 95% CI: 0.82-1.05, P = 0.24 for GG + GA vs AA).The meta-analysis suggests that the PDCD-1.5 (rs2227981) and PDCD-1.3 (rs11568821) polymorphisms are associated with susceptibility of cancer. Further studies with larger sample sizes are required to make a better assessment of the above association.
Project description:Epidemiological studies have demonstrated that interleukin-10 (IL-10) polymorphisms may be associated with the development of Behcet's disease (BD). However, the published results were inconsistent. Therefore, this meta-analysis was conducted to derive a more precise relationship between IL-10 polymorphisms and BD susceptibility. Online databases (PubMed, Embase, Science Citation Index (SCI), CNKI, and WanFang) were searched to identify eligible studies. Odds ratio (OR) and a 95% confidence interval (CI) were applied to assess the relationship strength between IL-10 -1082A>G (rs1800896), -819T>C (rs1800871), and -592A>C (rs1800872) polymorphisms and BD susceptibility. Publication bias, sensitivity, and cumulative analyses were conducted to measure the robustness of our findings. Finally, fifteen articles (36 independent case-control studies) involving 5,971 patients and 8,913 controls were included. Overall, significant associations between -819T>C polymorphisms and BD risk were observed in the total population (C vs. T: OR = 0.72, 95%CI = 0.67-0.77, P < 0.01, I 2 = 36.6%; TC vs. TT: OR = 0.73, 95%CI = 0.66-0.80, P < 0.01, I 2 = 23.0%; CC vs. TT: OR = 0.52, 95%CI = 0.39-0.70, P < 0.01, I 2 = 53.7%; TC+CC vs. TT: OR = 0.67, 95%CI = 0.61-0.71, P < 0.01, I 2 = 22.1%; and CC vs. TT+TC: OR = 0.66, 95%CI = 0.53-0.82, P < 0.01, I 2 = 57.8%). Moreover, the IL-10 -592 A>C polymorphism and the ACC haplotype exhibited a significant, protective effect against BD susceptibility. In summary, our meta-analysis suggested that IL-10 gene polymorphisms may play a salient role for BD development.
Project description:BACKGROUND: Published studies investigating the association between genetic polymorphism -884C/T (rs763110) of the FAS ligand (FASL) promoter and cancer risk reported inconclusive results. To derive a more precise estimation of the relationship, we performed an updated meta-analysis of all eligible studies. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a meta-analysis, including 47 studies with 19,810 cases and 23,485 controls, to confirm a more conclusive association between the FASL rs763110 polymorphism and cancer susceptibility. Overall, significantly reduced cancer risk was associated with the variant -884T when all studies were pooled (TC vs. CC: OR = 0.83, 95%CI = 0.75-0.92; P(heterogeneity)<0.001; TT+TC vs. CC: OR = 0.85, 95%CI = 0.77-0.94; P(heterogeneity)<0.001). Stratified analysis revealed that there was a statistically reduced cancer risk in Asians (TC vs. CC: OR = 0.76, 95%CI = 0.67-0.87; P(heterogeneity)<0.001; TT+TC vs. CC: OR = 0.79, 95%CI = 0.70-0.90; P(heterogeneity)<0.001) and in patients with cancers of head and neck (TC vs. CC: OR = 0.87, 95%CI = 0.77-0.99; P(heterogeneity) = 0.118; TT+TC vs. CC: OR = 0.88, 95%CI = 0.78-0.99; P(heterogeneity) = 0.168) and ovarian cancer (TC vs. CC: OR = 0.67, 95%CI = 0.49-0.90; P(heterogeneity) = 0.187; TT+TC vs. CC: OR = 0.64, 95%CI = 0.48-0.86; P(heterogeneity) = 0.199). Meta-regression showed that ethnicity (p = 0.029) and genotyping method (p = 0.043) but not cancer types (p = 0.772), sample size (p = 0.518), or source of controls (p = 0.826) were the source of heterogeneity in heterozygote comparison. CONCLUSION: Our results suggest that the FASL polymorphism rs763110 is associated with a significantly reduced risk of cancer, especially in Asian populations.
Project description:The complement factor I (CFI) gene polymorphisms have been reported to age-related macular degenerative (AMD) risk, nevertheless, above association is not consistent. We investigated a meta-analysis to evaluate the conclusions between CFI polymorphisms (rs10033900 and rs2285714) and AMD risk. An identification was covered with the PubMed and other databases through February 8, 2020. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations. After a comprehensive search, 11 different articles (12 case-control studies for total AMD and 11 case-control studies about neovascular disease/geographic atrophy in AMD) were retrieved. Individuals carrying C-allele or CC genotype of rs10033900 polymorphism may have a decreased risk to be AMD disease. For example, there has a significantly decreased relationship between rs10033900 polymorphism and AMD both in the whole group, Caucasian population and population-based source of control. Moreover, a similar trend in subgroup of genotype method group by MALDI-TOF MS was detected. To classify the type of AMD in further, decreased association was also observed in both neovascular disease and geographic atrophy AMD. No association was found about rs2285714 polymorphism. Our present groundbreaking study suggests that the CFI rs10033900 polymorphism is potentially associated with the risk of AMD development.
Project description:MicroRNAs (miRNAs or miRs) are a family of small non-coding RNAs that function as oncogenes or tumor suppressor genes. Recent evidence suggests that the pri-miR-34b/c rs4938723 variant is associated with the development of cancer. At present, there is an inconsistent association between the single-nucleotide polymorphism in pri-miR-34b/c and cancer in the limited studies. The present study is a case-control investigation, with 263 breast cancer (BC) patients and 221 control women, which examined the potential association of the pri-miR-34b/c rs4938723 polymorphisms with BC susceptibility. The polymorphisms were genotyped by the polymerase chain reaction restriction fragment length polymorphism method. No significant association between the pri-miR-34b/c rs4938723 variant and BC was identified [TC vs. TT: Odds ratio (OR), 0.87; 95% confidence interval (CI), 0.60-1.26; P=0.506; CC vs. TT: OR, 1.22; 95% CI, 0.61-2.47; P=0.600; TC+CC vs. TT: OR, 0.91; 95% CI, 0.64-1.31; P=0.648; CC vs. TT+TC: OR, 1.32; 95% CI, 0.67-2.59; P=0.498; C vs. T: OR, 0.99; 95% CI, 0.75-1.31; P=0.986]. However, a significant association was observed between the pri-miR-34b/c rs4938723 genotypes and clinicopathological characteristics, such a grade, progesterone receptor and human epidermal growth factor receptor 2 status were observed (P<0.05). These findings suggest that the pri-miR-34b/c rs4938723 variant may not be a risk factor for the development of BC.
Project description:PURPOSE: In the present work, the aim was to systematically review all studies about the association of vascular endothelial growth factor A (VEGF-A) polymorphisms with age-related macular degeneration (AMD) and to perform a meta-analysis. METHODS: Relevant studies were searched using PubMed, Embase, Wanfang (Chinese), VIP (Chinese), and the Chinese National Knowledge Infrastructure databases up to October, 2011. A meta-analysis was conducted using Stata software, version 11.0. RESULTS: A total of nine studies with 2,281 AMD cases and 2,820 controls met our eligibility criteria, and meta-analyses of four polymorphisms of the VEGF-A gene (rs1413711, rs833061, rs2010963, and rs3025039) were performed. This meta-analysis revealed moderate evidence supporting an association between the VEGF-A polymorphisms and AMD. For rs1413711, the TT genotype was associated with an increased risk of overall AMD (TT versus CT model, odds ratio (OR) 1.74, 95% confidence interval (CI) 1.22-2.48) and of wet AMD (TT versus CT model, OR 1.82, 95% CI 1.22-2.71; TT versus (CC+CT) model, OR 1.63, 95% CI 1.13-2.35). For rs833061, the C allele (C allele versus T allele, OR 1.72, 95% CI 1.00-2.96) and CC genotype (CC versus TT model, OR 1.77, 95% CI 1.00-3.11) were the risk factors for overall AMD, while the C allele was also associated with an increased risk of wet AMD (C allele versus T allele, OR 1.54, 95% CI 1.03-2.31). No association was observed between AMD risk and the variant genotypes of VEGF-A rs2010963 and rs3025039 polymorphisms in different genetic models. CONCLUSIONS: The results suggest the VEGF-A rs1413711 and rs833061 polymorphisms may contribute to AMD susceptibility.
Project description:Polymorphisms in one-carbon metabolism genes may influence the susceptibility to hepatocellular carcinoma (HCC). In the present study, we studied methylenetetrahydrofolate reductase (MTHFR) tagging polymorphisms in 584 HCC cases and 923 controls. Polymerase chain reaction was harnessed to detect MTHFR genotype. Overall, our results showed that genotype distribution of MTHFR rs4846048 and rs4845882 polymorphisms was not different between HCC patients and controls. MTHFR rs9651118 and rs1801133 loci were protective factors for HCC (rs9651118: CT vs. TT: adjusted odds ratio (OR) = 0.67, 95% confidence interval (CI): 0.49-0.90, P=0.008 and TC/CC vs. TT: adjusted OR = 0.70, 95% CI: 0.53-0.93, P=0.015; rs1801133: GA vs. GG: adjusted OR = 0.72, 95% CI: 0.54-0.97, P=0.031, AA/GA vs. GG: adjusted OR = 0.76, 95% CI: 0.57-0.99, P=0.045). However, MTHFR rs3753584 locus was a candidate for susceptibility to HCC (CT vs. TT: adjusted OR = 1.67, 95% CI: 1.20-2.32, P=0.003 and TC/CC vs. TT: adjusted OR = 1.59, 95% CI: 1.15-2.20, P=0.005). Results of haplotype analysis suggested that MTHFR Grs1801133Trs3753584Grs4845882Ars4846048Trs9651118 was associated with the risk of HCC (OR = 1.55, 95% CI: 1.16-2.07, P=0.003). The power of our study also confirmed these associations (the value of power >0.80). In summary, our findings suggested that MTHFR rs3753584, rs9651118 and rs1801133 polymorphisms may affect the risk of HCC in Chinese Han population. In future, our findings should be further validated in additional case-control studies.
Project description:Neuroblastoma is a pediatric malignancy arising from the developing peripheral nervous system. p53 and downstream effector miR-34b/c have critical tumor suppressing functions. TP53 Arg72Pro (rs1042522 C?>?G) and miR-34b/c rs4938723 (T?>?C) polymorphisms have been known to modify cancer susceptibility. This study was performed to validate the association of these two polymorphisms and neuroblastoma risk with 819 cases and 1780 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the strength of the associations. False positive report possibility analysis was adopted to dissect out real significant associations from chance findings. We found that both TP53 Arg72Pro (CG/GG vs. CC: adjusted OR?=?0.82, 95% CI?=?0.69-0.98) and miR-34b/c rs4938723 (TC/CC vs. TT: adjusted OR?=?0.64, 95% CI?=?0.54-0.75) were associated with decreased neuroblastoma susceptibility. Stratify analyses further confirmed the protective effect among some subgroups. Moreover, subjects with variant alleles of both polymorphisms were associated with more significantly decreased neuroblastoma risk (CG/TC vs. CC/TT: adjusted OR?=?0.38, 95% CI?=?0.28-0.50; GG/TC vs. CC/TT: adjusted OR?=?0.43, 95% CI?=?0.30-0.63) than those carrying variant allele of either one polymorphism (CC/TC vs. CC/TT: adjusted OR?=?0.51, 95% CI?=?0.37-0.69; CG/TT vs. CC/TT: adjusted OR?=?0.71, 95% CI?=?0.55-0.92), suggesting cumulative effects of the polymorphisms. False positive report possibility analysis further verified that our findings are noteworthy. Overall, we confirmed that miR-34b/c rs4938723 and TP53 Arg72Pro conferred decreased neuroblastoma risk and two polymorphisms exerted stronger protective effects against neuroblastoma than either one alone.
Project description:Molecular epidemiological studies have showed a closer association between microRNA polymorphisms with and head and neck cancer (HNC) risk. But the results of these studies were inconsistent. We performed this meta-analysis to clarify the associations between microRNA polymorphisms and HNC risk. Four electronic databases (PubMed, Embase, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between microRNA-146a rs2910164 G > C, microRNA-196a2 rs11614913 C > T, microRNA-149 rs2292832 C > T, microRNA-499 rs3746444 A > G polymorphisms and HNC risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power. Overall, 11 selected articles involving 16100 subjects were included in this meta-analysis. Significantly increased risk between microRNA-146a rs2910164 G > C polymorphism and HNC risk were observed in Caucasian population (GC vs. GG: OR = 1.31, 95%CI = 1.01-1.68; GC + CC vs. GG: OR = 1.26, 95%CI = 1.02-1.57). For microRNA-196a2 rs11614913 C > T, similarly increased risk were also found in Asian population (T vs. C, OR = 1.14, 95%CI = 1.04-1.25; TT vs. CC, OR = 1.33, 95%CI = 1.09-1.61; CT + TT vs. CC OR = 1.32, 95%CI = 0.99-1.76; TT vs. CC + CT, OR = 1.14, 95%CI = 0.99-1.33). In addition, no significant association was detected between microRNA-149 rs2292832 C > T and microRNA-499 rs3746444 A > G polymorphism and HNC risk. This meta-analysis demonstrates that microRNA polymorphisms are associated with HNC development based on ethnicity diversity.