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

Abstract

Background: 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.

Methods: Total 2,101 unrelated Han Chinese subjects were recruited, including 1,649 myopia and 452 control subjects. Five previously reported CC-associated gene variants (PDGFRA, MTOR, WNT7B, CMPK1 and RBP3) were genotyped by TaqMan assay, and their association with different myopia severity and ocular biometric parameters were evaluated.

Results: Joint additive effect analysis showed that MTOR rs74225573 paired with PDGFRA rs2114039 (P = .009, odds ratio (OR) = 4.91) or CMPK1 rs17103186 (P = .002, OR = 13.03) were significantly associated with higher risk in mild myopia. Critically, mild myopia subjects had significantly higher frequency in MTOR rs74225573 C allele than high myopia subjects (P = .003), especially in male subjects (P = .001, OR = 0.49). High myopia subjects carrying MTOR rs74225573 C allele have significant flatter CC (P = .035) and longer corneal radius (P = .044) than those carrying TT genotype.

Conclusion: This study revealed that male high myopia subjects are more prone to carry CC-related MTOR rs74225573 T allele, whereas mild myopia subjects are prone to carry the C allele. MTOR rs7422573 variant could be a genetic marker to differentiate mild from high myopia in risk assessment.

Abbreviations: 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.

Keywords: MTOR; Myopia; corneal curvature; genetic differentiation.