Complement factor H polymorphism in age-related macular degeneration

Ophthalmology. 2007 Jul;114(7):1327-31. doi: 10.1016/j.ophtha.2006.10.035. Epub 2007 Feb 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Complement Factor H / genetics*
  • Cross-Sectional Studies
  • Cytosine
  • Gene Frequency
  • Genotype
  • Histidine
  • Homozygote
  • Humans
  • Macular Degeneration / genetics*
  • Middle Aged
  • Polymorphism, Genetic*
  • Thymine
  • Tyrosine

Substances

  • Tyrosine
  • Histidine
  • Complement Factor H
  • Cytosine
  • Thymine