Translational Genomics Laboratory, Department of Biosciences, COMSATS University Islamabad, Pakistan.
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV.
Mol Vis. 2022 Oct 6;28:369-377. eCollection 2022.
Strabismus (STBMS) is a multifactorial ocular disorder in children that leads to misalignment of the eyes. Insulin-like growth factor 1 () has been shown to be involved in the development of extraocular muscles and myopia; however, data are limited on the genetic associations of with STBMS in Pakistan.
Two hundred seventy-four STBMS cases and 272 unaffected controls were recruited, and their DNA was extracted. Two single nucleotide polymorphisms, rs6214 and rs5742632, were genotyped using PCR-restriction fragment length polymorphism. Univariate logistic regression analysis was performed to determine the association of these single nucleotide polymorphisms with STBMS, and the results were adjusted for age and sex. In addition, 26 extraocular muscle tissues were collected from patients with STBMS undergoing squint correction surgery, along with 3 deceased control samples. mRNA expression was measured by quantitative PCR; the Mann-Whitney U test was applied, and fold change was calculated. Logistic regression analysis was applied to determine the association of RNA expression and fold change with genotype.
Multivariate logistic regression analysis revealed that rs5742632 (odds ratio [95% confidence interval] = 1.05[1.01-1.06], p = 0.03) is associated with STBM. Moreover, rs6214 (1.03[1.01-1.05], p = 0.03) and rs5742632 (1.09[1.04-1.11], p = 0.04) were associated with exotropia. Statistically, no significant difference in mRNA expression in the extraocular muscles between the STBMS cases and the controls was observed.
polymorphisms rs5742632 (A>G) and rs6214 (C>T) are plausible risk factors for the development of exotropia. However, the physiologic mechanism requires further evaluation.
斜视（STBMS）是一种导致眼球排列不正的儿童多因素眼部疾病。胰岛素样生长因子 1（）已被证明参与了眼外肌和近视的发育；然而，关于在巴基斯坦，与 STBMS 相关的遗传关联的数据有限。
招募了 274 例 STBMS 病例和 272 例无影响对照，并提取其 DNA。使用 PCR-限制性片段长度多态性对两个单核苷酸多态性 rs6214 和 rs5742632 进行基因分型。进行单变量逻辑回归分析，以确定这些单核苷酸多态性与 STBMS 的关联，并根据年龄和性别对结果进行调整。此外，从接受斜视矫正手术的 STBMS 患者中收集了 26 块眼外肌组织，以及 3 例已故对照样本。通过定量 PCR 测量 mRNA 表达；应用 Mann-Whitney U 检验，并计算折叠变化。应用逻辑回归分析确定 RNA 表达和折叠变化与基因型的关联。
多变量逻辑回归分析显示 rs5742632（比值比[95%置信区间] = 1.05[1.01-1.06]，p = 0.03）与 STBM 相关。此外，rs6214（1.03[1.01-1.05]，p = 0.03）和 rs5742632（1.09[1.04-1.11]，p = 0.04）与外斜视相关。统计学上，在 STBMS 病例和对照组之间，眼外肌中的 mRNA 表达没有显著差异。
多态性 rs5742632（A>G）和 rs6214（C>T）是外斜视发生的可能危险因素。然而，生理机制需要进一步评估。
