Association of polymorphisms in the <i>HTRA1</i> gene with myopia.

Abstract

To evaluate the associations of single-nucleotide polymorphisms (SNPs) in the <i>high-temperature requirement protease A 1</i> (<i>HTRA1)</i> gene with myopia. 25 SNPs in <i>HTRA1</i> were selected, including 23 haplotype-tagging SNPs, SNP rs2142308 from a previous genome-wide association study (GWAS) of myopia and rs11200638, a SNP strongly associated with age-related macular degeneration (AMD). All SNPs were genotyped in a Hong Kong Chinese cohort of 533 myopia subjects (including 175 high myopia, 189 moderate myopia and 189 mild myopia) and 280 non-myopic controls. The association of individual SNPs were evaluated in overall myopia and different subgroups of myopia using logistic regression. A tagging SNP, rs11200647, was significantly associated with myopia (p=2.17×10^-4, OR=0.67). Nominal associations were detected for the AMD-associated SNP rs11200638 (p=0.0042, OR=1.37) and tagging SNPs rs12266322 (p=0.0048, OR=0.59) and rs17103569 (p=0.047, OR=1.34). The association of rs11200647 with myopia remained significant after adjusting for rs11200638, rs12266322 and rs17103569. In sub-group analysis, two tagging SNPs, rs11200647 (p=2.24×10^-4, OR=0.58) and rs12266322 (p=8.31×10^-4, OR=0.39), showed significant association with moderate myopia. In haplotype association analysis, haplotypes AT (p=1.00×10^-4, OR=1.77) and haplotype GT (p=0.0019, OR=0.64), defined by rs11200647 and rs66884382, were significantly associated with myopia. This study provided new evidence to support <i>HTRA1</i> as an associated gene for myopia, especially moderate myopia. The findings suggested that myopia and AMD may have shared genetic components.