A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration

Zhenglin Yang, Nicola J. Camp, Hui Sun, Zongzhong Tong, Daniel Gibbs, D. Joshua Cameron, Haoyu Chen, Yu Zhao, Erik Pearson, Xi Li, Jeremy Chien, Andrew DeWan, Jennifer Harmon, Paul S. Bernstein, Viji Shridhar, Norman A. Zabriskie, Josephine Hoh, Kimberly Howes, Kang Zhang

Research output: Contribution to journalArticlepeer-review

615 Scopus citations


Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world and has a strong genetic predisposition. A locus at human chromosome 10q26 affects the risk of AMD, but the precise gene(s) have not been identified. We genotyped 581 AMD cases and 309 normal controls in a Caucasian cohort in Utah. We demonstrate that a single-nucleotide polymorphism, rs11200638, in the promoter region of HTRA1 is the most likely causal variant for AMD at 10q26 and is estimated to confer a population attributable risk of 49.3%. The HTRA1 gene encodes a secreted serine protease. Preliminary analysis of lymphocytes and retinal pigment epithelium from four AMD patients revealed that the risk allele was associated with elevated expression levels of HTRA1 mRNA and protein. We also found that drusen in the eyes of AMD patients were strongly immunolabeled with HTRA1 antibody. Together, these findings support a key role for HTRA1 in AMD susceptibility and identify a potential new pathway for AMD pathogenesis.

Original languageEnglish (US)
Pages (from-to)992-993
Number of pages2
Issue number5801
StatePublished - Nov 10 2006

ASJC Scopus subject areas

  • General


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