Age-related macular degeneration phenotypes associated with mutually exclusive homozygous risk variants in CFH and HTRA1 genes

Elaine W. Chong, Fakir M. Amirul Islam, Liubov D. Robman, Khin Zaw Aung, Andrea J. Richardson, Paul N. Baird, Robyn H. Guymer

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Purpose: To determine age-related macular degeneration (AMD) phenotypes associated with mutually exclusive homozygotic risk variants in rs1061170 (CFH) and rs11200638 (HTRA1). Methods: Nested case-control study of 2,982 eyes (2,129 control, 809 drusen ≥125 m, 44 advanced AMD) homozygous for CFH [TT (-/-) or CC (+/+) ] and HTRA1 [GG (-/-) or AA (+/+) ] were analyzed using logistic regression and generalized estimating equations specifically regards to homozygous risk variants in one but homozygous no-risk in the other gene. Results: In early AMD, [CFH +/+ HTRA1 -/- ] and [CFH -/- HTRA1 + / + ] were associated with central drusen (odds ratio [95% confidence interval] 4.13 [2.97-5.73] and 3.65 [1.88-7.09], respectively). However, only [CFH +/+ HTRA1 -/- ] was associated with central drusen occupying ≥50% area (13.9 [2.97-64.7]). In advanced AMD, [CFH +/+ HTRA1 -/- ] was associated with geographic atrophy (4.04 [1.57-10.4]), whereas [CFH -/- HTRA1 + / + ] was associated with neovascular AMD (36.5 [8.3-160.9]). In doubly homozygous risk groups [CFH +/+ HTRA1 + / + ], odds ratios were multiplicative. Conclusion: Central but not peripheral drusen location was strongly associated with both [CFH +/+ HTRA1 -/- ] and [CFH -/- HTRA1 + / + ]. Only [CFH +/+ HTRA1 -/- ] was significantly associated with increased central drusen area.

Original languageEnglish
Pages (from-to)989-998
Number of pages10
JournalRetina: the Journal of Retinal and Vitreous Diseases
Volume35
Issue number5
DOIs
Publication statusPublished - May 2015
Externally publishedYes

Keywords

  • age-related macular degeneration
  • ARMS2
  • CFH
  • drusen location
  • genes
  • genotype
  • HTRA1
  • phenotype
  • predictor models

Cite this