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Science. 2006 Nov 10;314(5801):992-3. Epub 2006 Oct 19.

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

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  • 1Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.

Abstract

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.

PMID:
17053109
[PubMed - indexed for MEDLINE]
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