Multilocus analysis of age-related macular degeneration

Julie Bergeron-Sawitzke, Bert Gold, Adam Olsh, Sarah Schlotterbeck, Kendal Lemon, Kala Visvanathan, Rando Allikmets, Michael Dean

Research output: Contribution to journalArticle

Abstract

Age-related macular degeneration (AMD) is a late onset vision disorder. Recent studies demonstrate that alterations in complement cascade genes are associated with AMD. Of the three identified complement loci, variants in complement factor H (CFH) have the highest impact as does an independent locus at 10q26. Our matched case-control study using the Age-Related Eye Disease Study (AREDS) cohort confirms and extends the associations in these loci. Subjects were genotyped for single nucleotide polymorphisms (SNPs) from CFH, complement component 2 (C2), complement component 3 (C3), complement factor B (CFB), age-related maculopathy susceptibility (ARMS2), HtrA serine peptidase 1 (HTRA1), and apolipoprotein E (APOE). Individual SNPs, and haplotypes showed risk trends consistent with those seen in other population studies for CFH, C3, C2, and CFB. SNP rs10490924 on chromosome 10 in exon 1 of the ARMS2 gene showed a highly significant association with an odds ratio (OR) of 3.2 (95% CI 2.4-4.2) for the risk allele and rs11200638 located in the proximal promoter region of HTRA1 showed a higher significant association with an OR of 3.4 (95% CI 2.5-4.6) with our AMD cases. We found that APOE haplotypes were not significantly associated with disease status. Adjustments for other risk factors did not significantly alter the observed associations. This study validates the complement pathway's involvement in AMD and suggests that allelic variants in complement genes have a direct role in disease. These results also support previous findings that variants in the region of 10q26 exert an independent risk for AMD.

Original languageEnglish (US)
Pages (from-to)1190-1199
Number of pages10
JournalEuropean Journal of Human Genetics
Volume17
Issue number9
DOIs
StatePublished - 2009

Fingerprint

Macular Degeneration
Complement Factor H
Single Nucleotide Polymorphism
Complement Factor B
Serine
Haplotypes
Complement C2
Odds Ratio
Genes
Chromosomes, Human, Pair 10
Complement C3
Eye Diseases
Apolipoproteins
Vision Disorders
Apolipoproteins E
Genetic Promoter Regions
Case-Control Studies
Exons
Peptide Hydrolases
Cohort Studies

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Bergeron-Sawitzke, J., Gold, B., Olsh, A., Schlotterbeck, S., Lemon, K., Visvanathan, K., ... Dean, M. (2009). Multilocus analysis of age-related macular degeneration. European Journal of Human Genetics, 17(9), 1190-1199. https://doi.org/10.1038/ejhg.2009.23

Multilocus analysis of age-related macular degeneration. / Bergeron-Sawitzke, Julie; Gold, Bert; Olsh, Adam; Schlotterbeck, Sarah; Lemon, Kendal; Visvanathan, Kala; Allikmets, Rando; Dean, Michael.

In: European Journal of Human Genetics, Vol. 17, No. 9, 2009, p. 1190-1199.

Research output: Contribution to journalArticle

Bergeron-Sawitzke, J, Gold, B, Olsh, A, Schlotterbeck, S, Lemon, K, Visvanathan, K, Allikmets, R & Dean, M 2009, 'Multilocus analysis of age-related macular degeneration', European Journal of Human Genetics, vol. 17, no. 9, pp. 1190-1199. https://doi.org/10.1038/ejhg.2009.23
Bergeron-Sawitzke J, Gold B, Olsh A, Schlotterbeck S, Lemon K, Visvanathan K et al. Multilocus analysis of age-related macular degeneration. European Journal of Human Genetics. 2009;17(9):1190-1199. https://doi.org/10.1038/ejhg.2009.23
Bergeron-Sawitzke, Julie ; Gold, Bert ; Olsh, Adam ; Schlotterbeck, Sarah ; Lemon, Kendal ; Visvanathan, Kala ; Allikmets, Rando ; Dean, Michael. / Multilocus analysis of age-related macular degeneration. In: European Journal of Human Genetics. 2009 ; Vol. 17, No. 9. pp. 1190-1199.
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