Ethnic differences in the association of SERPING1 with age-related macular degeneration and polypoidal choroidal vasculopathy

Abstract

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in the serpin peptidase inhibitor, clade G, member 1 (SERPING1) gene with neovascular AMD and PCV. Two haplotype-tagging SNPs, rs1005510 and rs11603020, of SERPING1 were genotyped in 708 unrelated Chinese individuals: 200 neovascular AMD, 233 PCV and 275 controls. A meta-analysis was also performed for all reported associations of SERPING1 SNPs with AMD and PCV. None of the tagging SNPs had a significant association with neovascular AMD or PCV (P > 0.05) in our study cohort. The meta-analyses showed that the most-studied SNP rs2511989 was not significantly associated with all forms of AMD, neovascular AMD, or PCV in East Asians (P = 0.98, 0.93 and 0.30, respectively) but was associated with AMD in Caucasians (P = 0.04 for all AMD and 0.004 for neovascular AMD). Therefore, the results of our study and meta-analysis suggest that SERPING1 is not a major genetic component of AMD or PCV in East Asians but is a genetic risk factor for AMD in Caucasians, providing evidence for an ethnic diversity in the genetic etiology of AMD.

Figure 1. Forest plots of meta-analysis for rs2511989 in (A) all forms of AMD, (B) neovascular AMD, and (C) PCV.

Individual and pooled odds ratios (OR) were estimated for the A allele. Squares indicate the study-specific OR. The size of the box is proportional to the percent weight that each study contributed in the pooled OR. Horizontal lines indicate 95% confidence intervals (CI). A diamond indicates the pooled OR with 95% CI. “Events” mean the counts of the A allele. “Total” means the total allele counts in cases or controls. “Weight” indicates how much an individual study contributes to the pooled estimate. “H-M” stands for the Mantel-Haenszel method in meta-analysis. “Random” indicates that a random-effects method was adopted for generating the meta-analysis result. AMD: age-related macular degeneration; PCV: polypoidal choroidal vasculopathy.

Figure 2. The forest plots of meta-analysis for rs1005510(G) in neovascular AMD.

Squares indicate study-specific odds ratios (ORs). The size of the box is proportional to the percent weight that each study contributed in the pooled OR. Horizontal lines indicate 95% confidence intervals (CI). A diamond indicates the pooled OR with 95% CI. “Events” mean the counts of the G allele. “Total” means the total allele counts in cases or controls. “Weight” indicates how much an individual study contributes to the pooled estimate. “H-M” stands for the Mantel-Haenszel method in meta-analysis. “Random” indicates that a random-effects method was adopted for generating the meta-analysis result. AMD: age-related macular degeneration.

Figure 3. The forest plot of meta-analysis for rs2511990(T) in AMD with all subtypes.

Squares indicate study-specific odds ratios (ORs). The size of the box is proportional to the percent weight that each study contributed in the pooled OR. Horizontal lines indicate 95% confidence intervals (CI). A diamond indicates the pooled OR with 95% CI. “Events” mean the counts of the T allele. “Total” means the total allele counts in cases or controls. “Weight” indicates how much an individual study contributes to the pooled estimate. “H-M” stands for the Mantel-Haenszel method in meta-analysis. “Fixed” indicates that a fixed-effects method was adopted for generating the meta-analysis result. AMD: age-related macular degeneration.

Figure 4. The forest plot of meta-analysis for rs11603020(C) in neovascular AMD.

Squares indicate study-specific odds ratios (ORs). The size of the box is proportional to the percent weight that each study contributed in the pooled OR. Horizontal lines indicate 95% confidence intervals (CI). A diamond indicates the pooled OR with 95% CI. “Events” mean the counts of the C allele. “Total” means the total allele counts in cases or controls. “Weight” indicates how much an individual study contributes to the pooled estimate. “H-M” stands for the Mantel-Haenszel method in meta-analysis. “Fixed” indicates that a fixed-effects method was adopted for generating the meta-analysis result. AMD: age-related macular degeneration.