Association between a functional genetic polymorphism (rs2230199) and age-related macular degeneration risk: a meta-analysis

Abstract

ABSTRACT. The association between the rs2230199 C>G single nucleotide polymorphism (SNP) in complement component 3 and agerelated macular degeneration (AMD) risk has been examined extensively but the results are not consistent among studies. The aim of this study was to perform a meta-analysis of all available studies on this SNP in relation to AMD. The comprehensive databases of PubMed, Medline, Web of Knowledge, CNKI, and Google Scholar were searched for case-control studies investigating the association between the rs2230199 polymorphism and AMD susceptibility. ORs with 95%CIs were estimated to assess the 12568 M.X. Zhang et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 12567-12576 (2015) association. Sensitivity analysis, test of heterogeneity, cumulative metaanalysis, and assessment of bias were also performed. A total of 15 published studies including 5593 cases and 5181 controls were used in this meta-analysis. Overall, the rs2230299 SNP was significantly associated with the risk of AMD in the overall population under the additive model (OR = 1.571, 95%CI = 1.414-1.745, P = 0.000), dominant model (OR = 1.681, 95%CI = 1.521-1.858, P = 0.000), and allelic model (OR = 1.597, 95%CI = 1.470-1.734, P = 0.000). In the subgroup analysis by ethnicity, the same results were found in Caucasian populations, while no significant correlations were found in Asian populations for all comparison models. In conclusion, our meta-analysis provides evidence that the rs2230199 polymorphism contributes to the development of AMD. Further large-scale multicenter epidemiological studies are warranted to confirm this finding.

Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

“…The glycine variant of C3 moves faster in electrophoresis and has been shown to confer increased adhesion to monocytes 21 . The R102G variant has shown a strong association with age-related macular degeneration (AMD) 20 22 23 . One feature indicating different C3 levels in those with type 1 diabetes is that children with type 1 diabetes have impaired clot lysis due to increased incorporation of C3 into clots thereby prolonging lysis time 24 .…”

Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine

“…The rs2230199 polymorphism, leading to the R102G substitution, is the most commonly investigated, since it seems to influence C3 binding capacity and cofactor activity, thereby extending convertase lifetime [ 111 ]. Overall, this polymorphism was associated with AMD risk, even though this finding was confirmed in Caucasians but not in Asians [ 112 ]. A further meta-analysis confirmed the increased AMD risk associated with rs2230199 polymorphism and suggested the adverse effect of rs1047286 and rs11569536 polymorphisms on the disease [ 113 ].…”

Associations of the intestinal microbiome with the complement system in age-related macular degeneration

“…Out of the genetic polymorphisms previously shown to be associated with risk for AMD [21][22][23][24][25][26][27][28][29][30][31][32][33][34], single nucleotide polymorphisms rs800292 (p = 0.0012), rs1410996 (p = 0.00019) and rs1061170 (p = 0.000064) within the complement factor H (CFH) gene and rs11200638 (p = 0.00012) within the high temperature requirement A serine peptidase 1 (HTRA1) gene were associated with a higher risk for having AMD in our cohort. However, rs12614 (p = 0.0057) within the complement factor B (CFB) gene was inversely correlated with AMD in the cohort (Fisher's exact test, Table 2).…”