Complement Factor H Polymorphism in Age-Related Macular Degeneration
Received 13 January 2006; accepted 25 October 2006. published online 15 February 2007.
Purpose
To determine the association between complement factor H (CFH) polymorphism T1277C (tyrosine-402 → histidine-402) and phenotypic variations of age-related macular degeneration (AMD).
Design
Cross-sectional observational study.
Participants
Subjects with dry or wet AMD and a control population consisting of age-matched non-AMD subjects from 2 clinical facilities examined during the period January 1, 1999 through December 31, 2002.
Methods
Total DNA isolated from the leukocytes of 66 AMD subjects and 58 age-matched control subjects was studied. The CFH gene was amplified by polymerase chain reaction and analyzed by Nla III restriction fragment length analysis.
Main Outcome Measures
Incidence of CHF polymorphism with the occurrence of AMD.
Results
Among the AMD patients, 15 had dry and 51 had wet AMD. For the CFH gene, the T1277C variant showed the genotype distribution as CC, TC, and TT. There was a strong association between homozygous C and AMD compared with the control population (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.32–8.74; P = 0.0053). Furthermore, dry AMD had a stronger association (OR, 8.32; 95% CI, 2.30–30.11; P = 0.001) than wet AMD (OR, 2.49; 95% CI, 0.90–6.84; P = 0.039) compared with the control population. Homozygous T was more prevalent in the control subjects compared with AMD patients (OR, 5; 95% CI, 2.18–11.43; P = 0.00005).
Conclusions
Complement factor H polymorphism T1277C (tyrosine-402 → histidine-402) is strongly associated with both dry and wet AMD and points to a possible role for inflammation in the pathogenesis of AMD.
1Department of Ophthalmology, University of California Irvine Medical Center, Irvine, California.
3Retina-Vitreous Associates Medical Group, Beverly Hills, California.
4University of Kansas School of Medicine, Kansas City, Kansas.
5Cedars-Sinai Medical Center, Los Angeles. California.
Correspondence to M. Cristina Kenney, MD, PhD, Department of Ophthalmology, University of California Irvine, Medical Center, 101 The City Drive, Orange CA 92868.
Manuscript no. 2006-83.
The authors have no commercial or proprietary interest in the products or companies mentioned in the article.
Supported by the Discovery Eye Foundation, Los Angeles, California; Henry L. Guenther Foundation, Los Angeles, California; Research to Prevent Blindness Foundation, New York, New York; and Skirball Molecular Ophthalmology Program, New York, New York.
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