Association of polymorphisms in theHTRA1gene with myopia

Purpose To evaluate the associations of single-nucleotide polymorphisms (SNPs) in the high-temperature requirement protease A 1 ( HTRA1) gene with myopia. Methods 25 SNPs in HTRA1 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. Results 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. Conclusions This study provided new evidence to support HTRA1 as an associated gene for myopia, especially moderate myopia. The findings suggested that myopia and AMD may have shared genetic components.