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

@article{Yang2006AVO,
  title={A Variant of the HTRA1 Gene Increases Susceptibility to Age-Related Macular Degeneration},
  author={Zhenglin Yang and Nicola J. Camp and Hui Sun and Zongzhong Tong and Daniel Gibbs and D. Joshua Cameron and H. Chen and Yu Zhao and Erik Pearson and Xi Li and Jeremy Chien and Andrew T Dewan and Jennifer Harmon and Paul S. Bernstein and Viji Shridhar and Norman A. Zabriskie and Josephine Hoh and Kim A Howes and Kang Zhang},
  journal={Science},
  year={2006},
  volume={314},
  pages={992 - 993}
}
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… Expand
Association of the HTRA1 gene variant with age-related macular degeneration in the Japanese population
TLDR
The hypothesis that the HTRA1 gene may increase susceptibility to AMD development and can participate in a potential new molecular pathway for AMD pathogenesis by extending this association across diverse ethnicities is supported. Expand
Further mapping of 10q26 supports strong association of HTRA1 polymorphisms with age-related macular degeneration
TLDR
It is demonstrated that rs11200638 in the promoter region and rs2293870 in exon 1 of HTRA1, are among the most significantly associated variants for advanced forms of AMD. Expand
An update on the genetics of age-related macular degeneration
TLDR
Variants within CFH and LOC387715/HTRA1 may contribute to the increased risk of late AMD largely through their impact on precursors, such as drusen and/or other RPE/Bruch's membrane changes. Expand
A polymorphism of LOC387715 gene is associated with age-related macular degeneration in the Japanese population
TLDR
It is shown that polymorphism of the LOC387715 gene is associated with AMD in Japanese as well as in Caucasians, and a disease odds ratio of 6.20 conferred by homozygosity for risk alleles at LOC 387715 compared with the non-risk genotype. Expand
Association of Htra1 gene polymorphisms with the risk of developing AMD in Iranian population.
TLDR
The results of this study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population. Expand
Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration.
TLDR
The genetic and functional evidence used to support either ARMS2 or HTRA1 as the causal gene for AMD risk is detailed, emphasizing both the historical development and the current understanding of the ARms2-HTRA1 locus in AMD pathogenesis. Expand
Chromosome 10q26 locus and age-related macular degeneration: a progress update.
TLDR
This review examines the recent progress and current uncertainty on the genetic and functional analyses of the 10q26 locus in AMD with a focus on ARMS2 and HTRA1. Expand
A novel ARMS2 splice variant is identified in human retina.
TLDR
Evidence that the HTRA1 polymorphism is functional and influences gene expression is inconsistent, combined with the observation that the ARMS2 rs10490924 variant changes the corresponding amino acid sequence of the protein, suggests that ARMS 2 is the more likely AMD gene in this region, although this continues to be debated in the literature. Expand
HTRA1 in Age-Related Macular Degeneration
TLDR
The pathology of AMD and the molecular function of the HtrA1 protein are summarized and a host of other genetic and environmental factors, known and unknown, is involved and warrants intensive future research. Expand
Assessment of the contribution of the LOC387715 gene polymorphism in a family with exudative age-related macular degeneration and heterozygous CFH variant (Y402H)
  • B. Shastry
  • Biology, Medicine
  • Journal of Human Genetics
  • 2007
TLDR
It is tempting to speculate that the combined effect of variants in the CFH and LOC 387715 genes may contribute to the AMD phenotype in this family, and further studies on these and other susceptibility genes may provide clues on variable phenotypes, new preventive strategies and treatment options for AMD. Expand
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A genome-wide screen for polymorphisms associated with age-related macular degeneration revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402 in the complement factor H gene. Expand
Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk
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It is reported 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. Expand
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It is shown that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium, implicating HF1 function in the pathogenetic mechanisms underlying AMD. Expand
Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration
TLDR
DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57, which likely explains ∼43% of AMD in older adults. Expand
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