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Margaret M. DeAngelis, PhD; Fei Ji, PhD; Ivana K. Kim, MD; Scott Adams, BS; Antonio Capone Jr, MD; Jurg Ott, PhD; Joan W. Miller, MD; Thaddeus P. Dryja, MD

Arch Ophthalmol. 2007;125(1):49-54.

Objective  To examine if the genes encoding complement factor H (CFH), apolipoprotein E (APOE), and elongation of very-long-chain fatty acids–like 4 (ELOVL4) confer risk of neovascular age-related macular degeneration (AMD) in an independent or interactive manner when controlling for smoking exposure.

Methods  We studied 103 unrelated patients with neovascular AMD who each had at least 1 sibling with normal maculae. Smoking histories were obtained. Genotyping was performed by analyzing amplified genomic fragments from CFH, APOE, and ELOVL4 by direct sequencing or by restriction endonuclease digests. Conditional logistic regression analysis was used to build a multifactor model.

Results  For CFH, only the CC genotype carried a statistically significant elevation of disease risk (odds ratio, 49.37; 95% confidence interval, 6.20-393.22; P<.001). No significant association was observed between neovascular AMD and APOE or ELOVL4. No significant interactions were found between smoking and having the CFH or APOE genotype nor were significant interactions found between the CFH, ELOVL4, and APOE genotypes.

Conclusions  Smoking and having the CFH CC genotype independently increase risk of neovascular AMD. APOE and ELOVL4 genotypes do not seem to modify risk.

Clinical Relevance  Smoking 10 pack-years or more and having the CFH CC genotype increase one's risk of neovascular AMD 144-fold compared with smoking less than 10 pack-years and having the CT or TT genotype.

Author Affiliations: Department of Ophthalmology, Harvard Medical School, and Massachusetts Eye and Ear Infirmary, Boston (Drs DeAngelis, Kim, Miller, and Dryja and Mr Adams); Laboratory of Statistical Genetics, Rockefeller University, New York, NY (Drs Ji and Ott); and Associated Retinal Consultants, PC, William Beaumont Hospital, Royal Oak, Mich (Dr Capone).

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