Genetic and Functional Dissection of HTRA1 and LOC387715 in Age-Related Macular Degeneration
نویسندگان
چکیده
A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.
منابع مشابه
LOC387715/HTRA1 gene polymorphisms and susceptibility to age-related macular degeneration: A HuGE review and meta-analysis
PURPOSE To examine the association of age-related macular degeneration (AMD) with HtrA serine peptidase 1 (HTRA1) gene rs11200638 G→A polymorphism and LOC387715/ ARMS2 gene rs10490924 G→T polymorphisms, and to evaluate the magnitude of the gene effect and the possible genetic mode of action. METHODS We searched the US National Library of Medicine's PubMed, Embase, OMIM, ISI Web of Science, an...
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PURPOSE Identification of genetic factors for age-related macular degeneration (AMD) is of crucial importance in this common cause of blindness. Exudative AMD is rapidly progressive and usually associated with severe prognosis. Our purpose was to investigate this association on locus 10q26 in a case-control study including French patients specifically affected with exudative AMD. METHODS Poly...
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10.2217/14750708.4.2.167 © 2 Evaluation of: Yang Z, Camp NJ, Sun H et al.: A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science 314(5801), 992–993 (2006) [1]. Age-related macular degeneration is a common cause of visual loss in the elderly, yet the genetic basis for this disease is poorly understood. Linkage studies show a major susceptibility locus ...
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PURPOSE Variants in complement factor H (CFH), the hypothetical LOC387715, and the high-temperature requirement A-1 (HTRA1) genes have been reported to be associated with age-related macular degeneration (AMD). The purpose of this study was to investigate the association of reported common single-nucleotide polymorphisms (SNPs) in CFH, LOC387715, and HTRA1 with exudative AMD in a northern Chine...
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