May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Assessment of Correlation Among Single Nucleotide Polymorphisms in Chromosome 10q26, HTRA1 Gene Expression Levels, and Clinical Characteristics of Neovascular Age Related Macular Degeneration
Author Affiliations & Notes
  • I. Chowers
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • M. Lederman
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • O. Weinstein
    Ophthalmology, Soroka University Medical Center, Beer Sheva, Israel
  • N. Goldenberg-Cohen
    Ophthalmology, Rabin Medical Center, Petah Tiqva, Israel
  • A. Lahad
    Family Medicine, Hadassah-Hebrew University School of Medicine, Jerusalem, Israel
  • A. Pollack
    Ophthalmology, Kaplan Medical Center, Rehovot, Israel
  • R. Axer-Siegel
    Ophthalmology, Rabin Medical Center, Petah Tiqva, Israel
  • J. Hoh
    Epidemiology and Public Health, Yale University, New Haven, Connecticut
  • D. J. Zack
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • T. Meir
    Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  • Footnotes
    Commercial Relationships I. Chowers, None; M. Lederman, None; O. Weinstein, None; N. Goldenberg-Cohen, None; A. Lahad, None; A. Pollack, None; R. Axer-Siegel, None; J. Hoh, None; D.J. Zack, None; T. Meir, None.
  • Footnotes
    Support BSF, ISF
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3009. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      I. Chowers, M. Lederman, O. Weinstein, N. Goldenberg-Cohen, A. Lahad, A. Pollack, R. Axer-Siegel, J. Hoh, D. J. Zack, T. Meir; Assessment of Correlation Among Single Nucleotide Polymorphisms in Chromosome 10q26, HTRA1 Gene Expression Levels, and Clinical Characteristics of Neovascular Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3009.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose:: Single nucleotide polymorphisms (SNPs) in chromosome 10q26 including rs10490924 and a variant in the promoter region of the HTRA1 gene (rs11200638) have been recently associated with age related macular degeneration (AMD). Our aim was to confirm the association among these SNPs and AMD in an independent population, to assess if rs11200638 affects HTRA1 mRNA levels, and to determine whether it accounts for heterogeneity in the clinical manifestations of neovascular AMD (NVAMD).

Methods:: DNA was extracted from 208 AMD patients and 100 age-matched controls. Genotyping for rs11200638 and rs10490924 was performed by restriction enzyme analysis and confirmed with sequencing. HTRA1 mRNA levels were measured in WBCs from 31 individuals with different rs11200638 genotypes using quantitative PCR. Genotypes were correlated with clinical characteristics of NVAMD and with outcome following photodynamic therapy (PDT).

Results:: Homozygosity (OR = 9.1, 95% CI = 3.4-24.3, P < 0.001) and heterozygosity (OR = 1.8, 95% CI = 1.1-3.2, P = 0.018) for the risk allele of rs10490924 were associated with AMD. Similarly, homozygosity (OR = 9.4, 95% CI = 2.2-40.6, P = 0.003) for the risk allele of rs11200638 (A variant) was associated with AMD while heterozygosity for this allele showed a trend towards association. The WBC mRNA levels of HTRA1 did not show evidence of a statistically significant correlation with the rs11200638 (HTRA1 upstream) SNP (mean expression level = 0.14 ± 0.16 and 0.25 ± 0.28 for the A and G alleles, respectively, P = 0.3). Neither SNPs were associated with characteristics of NVAMD such as choroidal neovascular membrane type or size, visual acuity, or outcome following PDT.

Conclusions:: The rs11200638 HTRA1 promoter variant and rs10490924 are associated with AMD in the Israeli population. However, rs11200638 is not associated with mRNA levels of HTRA1 in WBCs. Neither SNPs account for the variable clinical characteristics and response to PDT among NVAMD patients.

Keywords: age-related macular degeneration • genetics • clinical (human) or epidemiologic studies: risk factor assessment 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×