Cigarette smoking and APOE genotype interaction in age related macular degeneration

Abstract

Abstract: : Purpose: Age–related macular degeneration (AMD) is a leading cause of vision loss in older adults and is caused by a complex web of genetic and environmental factors. Two well replicated risk factors for AMD are history of cigarette smoking and APOE genotype. We have examined the joint effects of these factors in an ongoing genetic epidemiology study of AMD. Methods: Smoking history was determined in a data set of 302 cases with AMD (65% female, mean age 75.6) and 167 controls (58% female, mean age 68.1) by a self–administered questionnaire. Several measures of smoking, truncated at 10 years prior to study enrollment to control for temporal sequence of exposure and disease, were examined for association with AMD: lifetime smoking history (ever/never); current/past/never smoking; duration (years), intensity (cigarettes/day); latency (time since quitting); and a standard summary measure of duration and intensity (cigarette–years). APOE genotypes were determined using standard methods. Results: Only lifetime history was significantly associated with risk of AMD after adjusting for age and sex in a logistic regression model (OR=2.2; 95% CI: 1.4–3.5), p=0.0008). Consistent with previous data, APOE–2 was positively associated with AMD (OR=1.6; 95% CI: 0.8–3.0, p=0.2) and APOE–4 was negatively associated (OR=0.8; 95% CI: 0.5–1.3, p=0.3), although neither effect reached statistical significance in this data set. A borderline significant interaction between APOE–2 carrier status and lifetime smoking (p=0.05) suggested that smoking might modify the effect of APOE–2 on risk of AMD. Therefore, separate models were constructed in smokers and non–smokers. In smokers, APOE–2 was significantly associated with AMD (OR=3.3; 95% CI: 1.1–10.2], p=0.03), adjusting for age and sex. In non–smokers, no significant effect of APOE genotype was detected. Conclusions: The increase in the strength of association between APOE–2 and AMD in the presence of smoking denotes a potential synergistic effect of these two factors that increase risk of AMD. Further epidemiologic and experimental research into the effects of APOE–2 on risk of AMD should consider the effect of cigarette smoking as well.

Keywords: age–related macular degeneration • candidate gene analysis • clinical (human) or epidemiologic studies: risk factor assessment