Corneal curvature-associated MTOR variant differentiates mild myopia from high myopia in Han Chinese population

• Published in: Ophthalmic genetics Vol. 42; no. 4; pp. 446 - 457
• Main Authors: Yuan, Xiang-Ling, Zhang, Riping, Zheng, Yuqian, Sun, Lixia, Wang, Geng, Chen, Shaowan, Xu, Yanxuan, Chen, Shao-Lang, Qiu, Kunliang, Ng, Tsz Kin
• Format: Journal Article
• Language: English
• Published: England 01.08.2021
• Subjects: Adult; Aged; Alleles; Asians - genetics; Axial Length, Eye; Biometry; China - epidemiology; Cornea - pathology; Eye Proteins - genetics; Female; Genetic Association Studies; Genetic Markers; Genome-Wide Association Study; Genotyping Techniques; Humans; Male; Middle Aged; Myopia - diagnosis; Myopia - genetics; Myopia, Degenerative - diagnosis; Myopia, Degenerative - genetics; Nucleoside-Phosphate Kinase - genetics; Polymorphism, Single Nucleotide; Receptor, Platelet-Derived Growth Factor alpha - genetics; Refraction, Ocular; Retinol-Binding Proteins - genetics; TOR Serine-Threonine Kinases - genetics; Wnt Proteins - genetics; Young Adult; China; genetic differentiation; corneal curvature; MTOR; Myopia
• ISSN: 1381-6810; 1744-5094; 1744-5094
• DOI: 10.1080/13816810.2021.1923035

Myopia is the most prevalent ocular disorder in the world, and corneal parameters have been regarded as key ocular biometric parameters determining the refractive status. Here, we aimed to determine the association of genome-wide association study-identified corneal curvature (CC)-related gene variants with different severity of myopia and ocular biometric parameters in Chinese population. Total 2,101 unrelated Han Chinese subjects were recruited, including 1,649 myopia and 452 control subjects. Five previously reported CC-associated gene variants ( ) were genotyped by TaqMan assay, and their association with different myopia severity and ocular biometric parameters were evaluated. Joint additive effect analysis showed that rs74225573 paired with rs2114039 ( = .009, odds ratio (OR) = 4.91) or rs17103186 ( = .002, OR = 13.03) were significantly associated with higher risk in mild myopia. Critically, mild myopia subjects had significantly higher frequency in rs74225573 C allele than high myopia subjects ( = .003), especially in male subjects ( = .001, OR = 0.49). High myopia subjects carrying rs74225573 C allele have significant flatter CC ( = .035) and longer corneal radius ( = .044) than those carrying TT genotype. This study revealed that male high myopia subjects are more prone to carry CC-related rs74225573 T allele, whereas mild myopia subjects are prone to carry the C allele. rs7422573 variant could be a genetic marker to differentiate mild from high myopia in risk assessment. ACD: anterior chamber depth; AL: axial length; AL/CR: axial length/corneal radius ratio; ANOVA: analysis of variance; CC: corneal curvature; CCT: central corneal thickness; C.I.: confidence interval; CMPK1: cytidine/uridine monophosphate kinase 1; CR: corneal radius; D: diopter; GWAS: genome-wide association studies; HWE: Hardy-Weinberg equilibrium; LT: lens thickness; MIPEP: mitochondrial intermediate peptidase; MTOR: mechanistic target of rapamycin kinase; OR: odds ratio; PDGFRA: platelet-derived growth factor receptor-α; RBP3: retinol-binding protein 3; SD: standard deviation; SE: spherical equivalence; SNTB1: syntrophin beta 1; VCD: vitreous chamber depth; VIPR2: vasoactive intestinal peptide receptor 2; WNT7B: wingless/integrated family member 7B.