儿童近视严重程度和内表型的遗传关联。

Genetic associations of myopia severities and endophenotypes in children.

机构信息

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

出版信息

Br J Ophthalmol. 2021 Aug;105(8):1178-1183. doi: 10.1136/bjophthalmol-2020-316728. Epub 2020 Aug 14.

DOI:10.1136/bjophthalmol-2020-316728

PMID:32816751

Abstract

OBJECTIVE

To investigate the associations of multiple single-nucleotide polymorphisms (SNPs) with the severities and endophenotypes of myopia in children.

METHODS

A total of 3300 children aged 5-10 years were recruited: 137 moderate and high myopia (SE≤-3.0D), 670 mild myopia (-3.0D<SE≤-0.5D) and 2493 controls (SE>-0.5D). 13 SNPs in 13 genes/loci were selected for genotyping in all subjects using TaqMan assays. Associations between each SNP with myopia severities and ocular traits (spherical equivalent (SE), axial length (AL) and corneal radius (CR)) were analysed.

RESULTS

When compared with controls, SNPs rs4373767 (OR=1.15, p=0.038), rs7084402 (OR=1.18, p=0.005) and rs524952 (OR=1.14, p=0.025) showed nominal associations with overall myopia. rs4373767 and rs7084402 showed stronger associations with moderate and high myopia (rs4373767: OR=1.42, p=0.018; rs7084402: OR=1.33, p=0.025), while rs524952 had a stronger association with mild myopia (OR=1.14, p=0.025). rs524952 also showed a difference between emmetropia and hyperopia (p=0.018). In quantitative trait locus analysis, rs4373767, rs7744813 and rs524952 were correlated with both myopic SE (β=-0.09, p=0.03; β=-0.12, p=0.007; β=-0.13, p=0.0006, respectively) and AL (β=0.07, p=0.002; β=0.09, p=0.0008; β=0.07, p=0.0003, respectively). rs7839488 was correlated with both AL (β=0.07, p=0.005) and CR (β=0.02, p=0.006). Moreover, rs4373767-T (β=0.006; p=0.018), rs7744813-A (β=0.007; p=0.015) and rs524952-T (β=0.009; p=0.0006) were correlated with AL-CR ratio.

CONCLUSIONS AND RELEVANCE

and are genetic risk factors for moderate and high myopia, while and confer risk to excessive AL in children.

摘要

目的

探讨多个单核苷酸多态性（SNP）与儿童近视严重程度和内表型的相关性。

方法

共纳入 3300 名 5-10 岁的儿童：137 名中高度近视（SE≤-3.0D），670 名轻度近视（-3.0D<SE≤-0.5D）和 2493 名对照（SE>-0.5D）。采用 TaqMan 检测法对所有受试者的 13 个基因/位点的 13 个 SNP 进行基因分型。分析每个 SNP 与近视严重程度和眼表特征（等效球镜（SE）、眼轴长度（AL）和角膜半径（CR））之间的关系。

结果

与对照组相比，SNP rs4373767（OR=1.15，p=0.038）、rs7084402（OR=1.18，p=0.005）和 rs524952（OR=1.14，p=0.025）与总体近视有显著关联。rs4373767 和 rs7084402 与中高度近视的关联更强（rs4373767：OR=1.42，p=0.018；rs7084402：OR=1.33，p=0.025），而 rs524952 与轻度近视的关联更强（OR=1.14，p=0.025）。rs524952 在正视眼和远视眼之间也存在差异（p=0.018）。在数量性状基因座分析中，rs4373767、rs7744813 和 rs524952 与近视 SE（β=-0.09，p=0.03；β=-0.12，p=0.007；β=-0.13，p=0.0006）和 AL（β=0.07，p=0.002；β=0.09，p=0.0008；β=0.07，p=0.0003）均呈相关性。rs7839488 与 AL（β=0.07，p=0.005）和 CR（β=0.02，p=0.006）均呈相关性。此外，rs4373767-T（β=0.006；p=0.018）、rs7744813-A（β=0.007；p=0.015）和 rs524952-T（β=0.009；p=0.0006）与 AL-CR 比值呈相关性。