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  • Title: Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy.
    Author: Nakanishi H, Yamashiro K, Yamada R, Gotoh N, Hayashi H, Nakata I, Saito M, Iida T, Oishi A, Kurimoto Y, Matsuo K, Tajima K, Matsuda F, Yoshimura N.
    Journal: Invest Ophthalmol Vis Sci; 2010 Dec; 51(12):6183-7. PubMed ID: 20688737.
    Abstract:
    PURPOSE: To investigate whether the major genetic and environmental risk factors of age-related macular degeneration (AMD)-CFH Y402H and LOC387715 A69S and cigarette smoking-are also associated with polypoidal choroidal vasculopathy (PCV) and whether the associations of CFH Y402H and LOC387715 A69S with PCV are modified by smoking. METHODS: Three hundred seventy-five Japanese patients with PCV and 847 Japanese who served as population-based control subjects, all ≥55 years of age, were studied. CFH Y402H (rs1061170) and LOC387715 A69S (rs10490924) were genotyped with a single-nucleotide polymorphism (SNP) assay. An unconditional logistic regression model was used to analyze the association between age, sex, smoking status, CFH Y402H, LOC387715 A69S, and PCV. The synergy index (SI) was measured to assess gene-smoking and gene-gene interaction as a departure from additivity. RESULTS: CFH Y402H, LOC3387715 A69S, and cigarette smoking status were all significantly associated with PCV; for CFH Y402H, the adjusted odds ratio (OR) for the number of copies of the allele was 1.63 (95% confidence interval [CI], 1.12-2.36; P < 0.05); for LOC387715 A69S, the adjusted OR was 2.26 (95% CI, 1.83-2.78; P < 0.0001); and for smoking status (ever versus never smoked), the adjusted OR was 1.45 (95% CI, 1.00-2.10; P < 0.05). The joint effect of CFH Y402H and smoking was significantly greater than the additive scale, with an SI of 2.41 (95% CI, 1.14-5.10). CONCLUSIONS: CFH Y402H and LOC387715 A69S are both significantly associated with PCV. Cigarette smoking is an environmental risk factor for PCV. The findings suggest interactions between CFH 402H and cigarette smoking in PCV.
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