Complement factor H polymorphism in age-related macular degeneration

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 CHIF 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 polymorph ism 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.