Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular degeneration.
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.


CONCLUSIONS
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.
DeAngelis
Margaret M
MM
Department of Ophthalmology, Harvard Medical School, and Massachusetts Eye and Ear Infirmary, Boston, USA. margaret_deangelis@hms.harvard.edu
Ji
Fei
F
Kim
Ivana K
IK
Adams
Scott
S
Capone
Antonio
A
Ott
Jurg
J
Miller
Joan W
JW
Dryja
Thaddeus P
TP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D020256:Choroidal Neovascularization / Q000453:epidemiology* / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D016001:Confidence Intervals; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D017720:Molecular Epidemiology; D016017:Odds Ratio; D012307:Risk Factors; D035781:Siblings; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires
D001057:Apolipoproteins E; C493495:CFH protein, human; C418975:ELOVL4 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D017242:Complement Factor H