Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration

@article{Haines2005ComplementFH,
  title={Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration},
  author={Jonathan L. Haines and Michael A. Hauser and Silke Schmidt and William K. Scott and Lana M. Olson and Paul J. Gallins and Kylee L. Spencer and Shu Ying Kwan and Maher A. Noureddine and John R. Gilbert and Nathalie Schnetz-Boutaud and Anita Agarwal and Eric A. Postel and Margaret A. Pericak-Vance},
  journal={Science},
  year={2005},
  volume={308},
  pages={419 - 421}
}
Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring a susceptibility locus for AMD. We used single-nucleotide polymorphisms to interrogate this region and identified a strongly associated haplotype in two independent data sets. DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant, Y402H, that… Expand
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References

SHOWING 1-10 OF 52 REFERENCES
Age-Related Macular Degeneration: A High-Resolution Genome Scan for Susceptibility Loci in a Population Enriched for Late-Stage Disease
TLDR
The results consolidate the chromosomal locations of several AMD susceptibility loci and, together with previous reports, should facilitate the search for disease-associated sequence variants. Expand
Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family.
TLDR
RT-PCR analysis demonstrated that exon 104 of HEMICENTIN-1 is alternatively spliced in various cell types, which supports the conclusion that HEMicentIN- 1 is the ARMD1 gene. Expand
Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies.
TLDR
Transgenic and knockout studies have provided important mechanistic insights into the development of choroidal neovascularization, the principal cause of vision loss in age-related macular degeneration, and this in turn has culminated in preclinical and clinical trials of directed molecular interventions. Expand
Association Between C-Reactive Protein and Age-Related Macular Degeneration
TLDR
The results suggest that elevated CRP level is an independent risk factor for AMD and may implicate the role of inflammation in the pathogenesis of AMD. Expand
Genetic influence on early age-related maculopathy: a twin study.
TLDR
This study confirms a significant genetic influence in ARM and suggests that future genetic studies should examine phenotypes of large (> or =125 microm) soft drusen and > or =20 hard drusan, because these seem to be the most heritable components. Expand
Drusen associated with aging and age‐related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease
  • R. Mullins, S. Russell, Don H. Anderson, G. Hageman
  • Chemistry, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2000
TLDR
Drusen associated with aging and age‐related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. Expand
Dissection of genomewide-scan data in extended families reveals a major locus and oligogenic susceptibility for age-related macular degeneration.
TLDR
Evidence for a major ARMD locus on 15q21, which, coupled with numerous other loci segregating in these families, suggests complex oligogenic patterns of inheritance for ARMD. Expand
Genetic risk of age-related maculopathy. Population-based familial aggregation study.
TLDR
The findings indicate that approximately one fourth of all late ARM is genetically determined and suggest that genetic susceptibility may play an important role in determining the onset of disease. Expand
Age-related maculopathy: a genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions.
TLDR
The interesting hypothesis that the effect of smoking on the risk of ARM is accentuated by a gene in the 10q26 region--a region implicated by four other studies is generated. Expand
A pooled case-control study of the apolipoprotein E (APOE) gene in age-related maculopathy
TLDR
Data confirm that the APOE-4 allele, or an allele in linkage disequilibrium with it, reduces the risk of age-related maculopathy and suggest that the effect of the APoe-2 allele may vary by gender, and thatAPOE-2 may confer an increased risk only to males. Expand
...
1
2
3
4
5
...