A Variant of the HTRA1 Gene Increases Susceptibility to Age-Related Macular Degeneration

• DOI: 10.1126/science.1133811
• Publication Date: 2006-10-20T01:28:20Z
• Authors: 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
• Keywords: Drusen; Genetic predisposition

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