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American Journal of Epidemiology Advance Access originally published online on December 13, 2008
American Journal of Epidemiology 2009 169(5):633-641; doi:10.1093/aje/kwn358
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Combined Effects of Complement Factor H Genotypes, Fish Consumption, and Inflammatory Markers on Long-Term Risk for Age-related Macular Degeneration in a Cohort

Jie Jin Wang, Elena Rochtchina, Wayne Smith, Ronald Klein, Barbara E. K. Klein, Tripti Joshi, Theru A. Sivakumaran, Sudha Iyengar and Paul Mitchell

Correspondence to Dr. Jie Jin Wang, Centre for Vision Research, Department of Ophthalmology, University of Sydney, Westmead Hospital, Hawkesbury Road, Westmead, NSW 2145, Australia (e-mail: jiejin_wang{at}wmi.usyd.edu.au).

Received for publication March 6, 2008. Accepted for publication October 13, 2008.

At baseline in 1992–1994, the authors assessed the combined effects of complement factor H (CFH) genotypes with smoking, fish consumption, and inflammatory markers on the risk of age-related macular degeneration (AMD) in 3,654 persons aged ≥49 years. They reexamined 75% of the survivors after 5 and 10 years, confirming incident AMD by side-by-side photographic grading. Of the 2,452 persons followed in the Blue Mountains Eye Study, 1,881 were genotyped (rs1061170), with CC, CT, and TT identified in 13.6%, 46.7%, and 39.7%, respectively. AMD risk increased with each additional C allele (early AMD: age- and sex-adjusted relative risk (RR) = 1.6, 95% confidence interval (CI): 1.2, 1.9; late AMD: RR = 2.3, 95% CI: 1.5, 3.6). Late AMD risk among current smokers with the CC/CT genotypes (RR = 10.7, 95% CI: 3.4, 33.9) was 5-fold that for genotypically similar nonsmokers (RR = 2.2, 95% CI: 0.9, 5.5) versus current nonsmokers with TT genotypes. Weekly compared with less than weekly consumption of fish was associated with reduced late AMD risk in participants with the CC genotype (RR = 0.15, 95% CI: 0.03, 0.8) but not the CT (RR = 0.7, 95% CI: 0.3, 2.0) or TT (RR = 1.3, 95% CI: 0.2, 7.2) genotypes. This study documents joint contributions from genetic and systemic factors in determining the progression of AMD.

cohort studies; complement factor H; environmental exposure; genetics; macular degeneration; seafood; smoking

Abbreviations: AMD, age-related macular degeneration; BMES, Blue Mountains Eye Study; CFH, complement factor H; CI, confidence interval; RPE, retinal pigment epithelium; RR, relative risk


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