Association of combined cigarette smoking and ARMS2/LOC387715 A69S polymorphisms with age-related macular degeneration: A meta-analysis

ABSTRACT

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 combined ARMS2/LOC387715 genotypes 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 of ARMS2/LOC387715 and smoking in AMD pathogenesis which may be the complement system pathway.

KEYWORDS:

• Age-related macular degeneration (AMD)
• ARMS2/LOC387715 A69S
• cigarette smoking
• mechanism of pathogenesis
• meta-analysis
• rs10490924
• synergistic effect

Acknowledgments

The authors would like to express their greatest appreciation to all the participants in the study, especially to Dr. Zou G. Y. from the Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, and Robarts Clinical Trials Inc. for providing necessary information and interaction analysis software.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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