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. 2008;14:2263-71.
Epub 2008 Dec 8.

Sequence Variants in HTRA1 and LOC387715/ARMS2 and Phenotype and Response to Photodynamic Therapy in Neovascular Age-Related Macular Degeneration in Populations From Israel

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Free PMC article

Sequence Variants in HTRA1 and LOC387715/ARMS2 and Phenotype and Response to Photodynamic Therapy in Neovascular Age-Related Macular Degeneration in Populations From Israel

Itay Chowers et al. Mol Vis. .
Free PMC article

Abstract

Purpose: Single nucleotide polymorphisms (SNPs) in the tightly linked LOC387715/ARMS2 and HTRA1 genes have been associated with age-related macular degeneration (AMD). We tested whether these SNPs are associated with AMD in Israeli populations, if they underlie variable phenotype and response to therapy in neovascular AMD (NVAMD), and if HTRA1 expression in vivo is associated with its promoter variant.

Methods: Genotyping for the rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 was performed on 255 NVAMD patients and 119 unaffected controls from Ashkenazi and Sephardic Jewish, and from Arab origins which are the main ethnic groups composing the Israeli population. Genotyping was correlated with phenotype and response to therapy among 143 patients who underwent photodynamic therapy (PDT). HTRA1 mRNA levels in white blood cells (WBCs), measured by quantitative PCR, were correlated with genotype in 27 participants.

Results: Both SNPs were in almost complete linkage disequilibrium (D'=0.96-1). Homozygotes for the T allele of rs10490924 had an odds ratio (OR) of 8.6, with a 95% confidence interval (CI) of 3.5-20.8, and homozygotes for the A allele of rs11200638 had an OR of 10.7, with a 95% CI of 3.2-35.7, for having AMD (p<0.00001). There was no association among these SNPs and phenotype or response to PDT. HTRA1 mRNA levels in WBCs were not associated with rs11200638 genotypes.

Conclusions: The rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 are strongly associated with NVAMD in this Israeli population. These variants do not have a major contribution to the variable phenotype and response to PDT which characterize NVAMD.

Figures

Figure 1
Figure 1
Relative expression levels of HTRA1 in NVAMD patients and unaffected controls. A: Shown are expression levels in white blood cells according to rs11200638 genotypes in individuals homozygous for the wild-type allele (GG, n=13), participants homozygous for the risk allele (AA, n=6), and in heterozygous participants (AG, n=8). Differences between the three groups were not significant (p>0.1 for each comparison). B: Shown are mRNA levels of HTRA1 in 22 NVAMD patients and 5 unaffected individuals (p=0.9). In both A and B, RQ represents relative HTRA1 mRNA levels. Error bars represent standard deviation (SD).

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