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G. C. Wong, H. Chen, V. S. Hau, Z. Yang, D. Gibbs, X. Yang, P. Zhao, X. Ma, J. Zeng, K. Zhang; Association of HTRA1 Polymorphism and Bilaterality in Advanced Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2661.
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Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in elderly people. Recently, a single nucleotide polymorphism (SNP), rs11200638, in the promoter of the HTRA1 gene was found to be associated with wet and dry forms of AMD. The purpose of this study is to investigate the association of rs11200638 with bilateral and unilateral wet AMD.
AMD patients and age matched controls were enrolled and genotyped for the rs11200638 polymorphism. AMD patients were classified as bilateral wet AMD, unilateral wet AMD, bilateral dry AMD and unilateral dry AMD. Wet AMD eyes were also classified according to choroidal neovascularization subtype including classic, occult and mixed choroidal neovascularization. Allele frequencies and genotype frequencies were compared among different phenotype groups by a chi square test. Odds ratios (OR) and 95% confidence intervals were calculated to estimate risk
The A allele and AA genotype of rs11200638 were significantly more prevalent in bilateral wet AMD patients than unilateral wet AMD patients (p=0.04 and 0.03, respectively, chi square test). The homozygote OR of binocular wet AMD (12.41; 95% CI, 5.70-27.03) was 1.95 fold greater than that of monocular wet AMD (6.36; 95% CI, 2.98-13.55). The same trend was seen in dry AMD. There is no significant difference of allele or genotype frequencies among the subtypes of choroidal neovascularization.
The SNP rs11200638 in the promoter of HTRA1 was associated with bilaterality of AMD. The risk allele A conferred higher risk for binocular AMD than monocular AMD. This is consistent with the role of HTRA1 in the pathogenesis of AMD. Further study of HTRA1 will provide more insight into the pathogenesis of AMD.
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