Liu Linjie, He Juan, Lu Xiaoyan, Yuan Yimin, Jiang Dandan, Xiao Haishao, Lin Shudan, Xu Liangde, Chen Yanyan
School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, China.
Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Front Cell Dev Biol. 2021 Apr 28;9:628182. doi: 10.3389/fcell.2021.628182. eCollection 2021.
Myopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-β signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children.
A total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the rs10760673 and rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase.
A total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: ' = 0.022; dominant: ' = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of were associated with a significant myopic shift (additive: ' = 0.008; dominant: ' = 0.028; recessive: ' = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (' = 0.013, β = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (' = 0.031, β = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak.
The present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the and genes with myopia may be mediated by the TGF-β signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr.org.cn.
近视是一种复杂的多因素疾病，涉及由不同基因介导的多个重叠信号通路。这项前瞻性队列研究评估了转化生长因子-β（TGF-β）信号通路中的两个基因变异与中国学龄儿童近视的发生、进展以及眼部生物测量参数之间的关联。
共检查了556名二年级儿童，并对其进行了3.5年的随访。每年测量非散瞳验光和眼部生物测量参数。采用多变量回归分析评估rs10760673和rs7550232变异对近视发生和进展的影响。使用10000次置换检验来校正多重检验。使用RegulomeDB、HaploReg和rVarBase对单核苷酸多态性（SNP）进行功能注释。
共有448名儿童纳入分析。在对性别、年龄、近距离工作时间和户外活动时间进行调整并进行10000次置换后，结果表明，rs7550232的C等位基因以及与 相邻的AC或CC基因型在两种遗传模型中均与近视发病风险显著增加相关（加性模型：' = 0.022；显性模型：' = 0.025）。此外，rs10760673的A等位基因以及AA或AG基因型与显著的近视性屈光度变化相关（加性模型：' = 0.008；显性模型：' = 0.028；隐性模型：' = 0.027）。此外，rs10760673与眼轴长度（AL）增加相关（' = 0.013，β = 0.03）以及AL与角膜曲率半径之比（AL/CRC）变化相关（' = 0.031, β = 0.003）。使用RegulomeDB、HaploReg和rVarBase进行的分析表明，rs7550232可能影响转录因子结合、任何基序、DNase足迹和DNase峰。
本研究表明，rs10760673和rs7550232可能分别代表学龄儿童近视进展和发病的易感基因座。 和 基因变异与近视的关联可能由TGF-β信号通路介导；这一假设需要在功能研究中进行验证。本试验在www.Chictr.org.cn上注册为ChiCTR190
