Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, Guangdong, China.
Shantou University Medical College, Shantou, Guangdong, China.
Ophthalmic Genet. 2021 Aug;42(4):446-457. doi: 10.1080/13816810.2021.1923035. Epub 2021 May 12.
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.
近视是世界上最常见的眼部疾病，角膜参数被认为是决定屈光状态的关键眼部生物计量学参数。在这里，我们旨在确定全基因组关联研究鉴定的与角膜曲率（CC）相关的基因变异与中国人群中不同严重程度的近视和眼部生物计量学参数的关联。
共纳入 2101 名无关汉族个体，包括 1649 名近视患者和 452 名对照组。采用 TaqMan 检测法对 5 个先前报道的与 CC 相关的基因变异（rs74225573、rs2114039、rs17103186、rs10757278 和 rs25487）进行基因分型，并评估它们与不同近视严重程度和眼部生物计量学参数的关系。
联合加性效应分析显示，rs74225573 与 rs2114039（ = 0.009，优势比（OR）= 4.91）或 rs17103186（ = 0.002，OR = 13.03）的双等位基因显著增加轻度近视的发病风险。重要的是，轻度近视患者的 rs74225573 C 等位基因频率明显高于高度近视患者（ = 0.003），尤其是男性（ = 0.001，OR = 0.49）。携带 rs74225573 C 等位基因的高度近视患者的 CC 更平坦（ = 0.035），角膜半径更长（ = 0.044）。
本研究表明，男性高度近视患者更易携带与 CC 相关的 rs74225573 T 等位基因，而轻度近视患者更易携带 C 等位基因。rs7422573 变异可能是区分轻度和高度近视风险评估的遗传标志物。
ACD：前房深度；AL：眼轴长度；AL/CR：眼轴/角膜半径比值；ANOVA：方差分析；CC：角膜曲率；CCT：中央角膜厚度；C.I.：置信区间；CMPK1：胞苷/尿苷单磷酸激酶 1；CR：角膜半径；D：屈光度；GWAS：全基因组关联研究；HWE：哈迪-温伯格平衡；LT：晶状体厚度；MIPEP：线粒体中间肽酶；MTOR：雷帕霉素靶蛋白激酶；OR：优势比；PDGFRA：血小板衍生生长因子受体-α；RBP3：视黄醇结合蛋白 3；SD：标准差；SE：球镜等效；SNTB1：联蛋白β 1；VCD：玻璃体腔深度；VIPR2：血管活性肠肽受体 2；WNT7B：无翅型整合素家族成员 7B。
