Elsevier

Ophthalmology

Volume 118, Issue 2, February 2011, Pages 339-344
Ophthalmology

Original article
Complement Factor H Y402H Variant and Risk of Age-Related Macular Degeneration in Asians: A Systematic Review and Meta-Analysis

https://doi.org/10.1016/j.ophtha.2010.06.040Get rights and content

Purpose

To investigate whether the Y402H variant in the complement factor H gene is associated with age-related macular degeneration (AMD) in Asian populations.

Design

Meta-analysis of previous publications.

Participants

Case-control groups of subjects with AMD and controls from 13 association studies.

Methods

We performed a meta-analysis of the association between Y402H and AMD in Asian populations using data available from 13 case-control studies involving 3973 subjects. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed- and random-effects models. The Q-statistic test was used to assess heterogeneity, and Egger's test was used to evaluate publication bias. Sensitivity analysis, cumulative meta-analysis, and meta-regression analysis were also performed.

Main Outcome Measures

Allele and genotype frequencies of the Y402H variant.

Results

The Y402H variant showed a significant summary OR of 1.97 (95% CI, 1.54–2.52; P<0.001; allelic contrast model) per allele. Possession of at least 1 copy of the C allele increased the disease risk by 1.97-fold (95% CI, 1.63–2.39; P<0.001; dominant model) and accounted for 8.8% of the attributable risk of AMD in Asian populations. Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Meta-regression analysis indicated no significant effect of baseline study characteristics on the summary effect size. Cumulative meta-analysis revealed that the summary ORs were stable and the 95% CIs narrowed with the accumulation of data over time.

Conclusions

Our analysis provides substantial evidence that the Y402H variant is significantly associated with AMD in Asian populations. Our results expand the number of confirmed AMD susceptibility loci for Asians populations, which provide a better understanding of the genetic architecture underlying disease susceptibility and may advance the potential for preclinical prediction in future genetic tests by a combined evaluation of inherited susceptibility with previously established loci.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Identification and Eligibility of Relevant Studies

We performed a systematic PubMed literature search (up to January 2010) using the search terms “macular degeneration” AND “complement factor H” OR “CFH” as described in a previously published meta-analysis of the Y402H variant in European populations.27 The literature search was performed in duplicate by 2 authors (NK and HB).

Studies included in the meta-analysis had to fulfill the following criteria: (1) The study must be unrelated case control or population based, representing an assessment

Eligibility of Studies

A total of 276 publications were identified in the initial PubMed search, of which 13 met our inclusion criteria. Table 1 lists the studies included in the meta-analysis together with summary characteristics of study subjects. The combined sample size for this meta-analysis was 3973.

Allele Frequency

Allele and genotype distributions for the Y402H variant from individual studies are shown in Table 2 (available at http://aaojournal.org). None of the 13 studies demonstrated significant deviation from the

Discussion

The low frequency of variant alleles and small sample sizes in studies have hindered reliable assessment of the association between CFH Y402H and AMD in Asian populations. To overcome these barriers, we performed a systematic meta-analysis of 13 case-control studies involving 3973 subjects.

This meta-analysis showed an allelic summary OR of 1.97 (P<0.001) and strongly supported the notion that the Y402H variant is a risk factor for AMD in Asian populations. In individuals carrying at least 1

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    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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