Association of polymorphisms in the HTRA1 gene with myopia

• Published in: British journal of ophthalmology Vol. 109; no. 4; pp. 456 - 462
• Main Authors: Chen, Shu Ying, Xu, You Mei, Tam, Pancy O S, Pang, Chi Pui, Tham, Clement C, Yam, Jason C, Chen, Li Jia
• Format: Journal Article
• Language: English
• Published: BMA House, Tavistock Square, London, WC1H 9JR BMJ Publishing Group Ltd 01.04.2025; BMJ Publishing Group LTD
• Subjects: Adult; Age; Age-Related Macular Degeneration; Aged; Demographics; Disease; East Asian People - genetics; Female; Genetic eye disease; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Genotype; Genotyping Techniques; Haplotypes; High-Temperature Requirement A Serine Peptidase 1 - genetics; Hong Kong - epidemiology; Humans; Macular degeneration; Male; Middle Aged; Myopia; Myopia - genetics; Optics and Refraction; Polymorphism; Polymorphism, Single Nucleotide; Population; Regression analysis; Risk Factors; Hong Kong; Genetics; Age-Related Macular Degeneration; Optics and Refraction; Risk Factors
• ISSN: 0007-1161; 1468-2079; 1468-2079
• DOI: 10.1136/bjo-2024-325935

PurposeTo evaluate the associations of single-nucleotide polymorphisms (SNPs) in the high-temperature requirement protease A 1 (HTRA1) gene with myopia.Methods25 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.ResultsA 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.ConclusionsThis 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.