<i>HTRA1</i> Promoter Polymorphism in Wet Age-Related Macular Degeneration

TLDR

Age‑related macular degeneration, the leading cause of irreversible vision loss after age 50, is divided into wet and dry forms, with inherited complement factor H variants strongly linked to drusen in dry AMD. A whole‑genome association study in a Chinese cohort identified a promoter SNP in HTRA1 with a P value <10^−11. The risk allele of this HTRA1 promoter SNP confers a ten‑fold increased likelihood of developing wet AMD compared with the wild‑type genotype.

Abstract

Age-related macular degeneration (AMD), the most common cause of irreversible vision loss in individuals aged older than 50 years, is classified as either wet (neovascular) or dry (nonneovascular). Inherited variation in the complement factor H gene is a major risk factor for drusen in dry AMD. Here we report that a single-nucleotide polymorphism in the promoter region of HTRA1, a serine protease gene on chromosome 10q26, is a major genetic risk factor for wet AMD. A whole-genome association mapping strategy was applied to a Chinese population, yielding a P value of <10(-11). Individuals with the risk-associated genotype were estimated to have a likelihood of developing wet AMD 10 times that of individuals with the wild-type genotype.