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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.
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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).
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).
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.
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.
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