Jeoung Jin Wook, Kim Dong Myung, Oh Sohee, Lee Jee-Soo, Park Sung Sup, Kim Ji Yeon
Departments of *Ophthalmology ‡Laboratory Medicine §Biomedical Research Institute, Seoul National University Hospital †Department of Biostatistics, Seoul National University Boramae Hospital, Seoul, Korea.
J Glaucoma. 2017 Nov;26(11):1030-1035. doi: 10.1097/IJG.0000000000000751.
We investigated whether polymorphisms of the endothelial NO synthase (eNOS) gene are associated with normal tension glaucoma (NTG). We also investigated whether the eNOS polymorphisms are associated with NTG subgroups [NTG with and without optic disc hemorrhage (DH)].
A total of 251 patients with NTG and 245 healthy volunteers were enrolled in this study. DNA from peripheral blood leukocytes was extracted, and the genotypes of 4 polymorphisms (rs2070744, rs1549758, rs1799983, and rs2566514) in the eNOS gene were determined using restriction fragment length polymorphism and the SNaPshot method. The primary outcome was to investigate the relation between eNOS polymorphisms and NTG. The secondary outcome was to compare the frequencies of the polymorphic genotypes among the NTG subgroups. Bonferroni correction was used to adjust for type I error.
In all subjects, the genotype distribution was in accordance with Hardy-Weinberg equilibrium. None of the 4 polymorphisms showed any significant difference in the frequencies of alleles or genotypes between the NTG patients and controls. In the further analysis comparing the genotypic frequencies between NTG with DH and normal controls, the CC/CT genotype of rs2070744 was significantly associated with DH in NTG patients (genotypic association test, P-value=0.0041). On the multiple logistic regression analysis adjusted for covariates such as sex and age, the NTG with DH was associated with polymorphic genotypes of rs2070744 with a borderline significance (additive genetic model, P=0.0070).
Our results indicates that eNOS rs2070744 can be associated with NTG patients with DH. This finding suggests that the eNOS polymorphism may be a genetic risk factor in the development of DH in NTG patients.
我们研究了内皮型一氧化氮合酶（eNOS）基因多态性是否与正常眼压性青光眼（NTG）相关。我们还研究了eNOS基因多态性是否与NTG亚组[有无视盘出血（DH）的NTG]相关。
本研究共纳入251例NTG患者和245名健康志愿者。提取外周血白细胞的DNA，采用限制性片段长度多态性和SNaPshot方法测定eNOS基因中4种多态性（rs2070744、rs1549758、rs1799983和rs2566514）的基因型。主要结果是研究eNOS基因多态性与NTG的关系。次要结果是比较NTG亚组中多态性基因型的频率。采用Bonferroni校正来调整I型错误。
在所有受试者中，基因型分布符合Hardy-Weinberg平衡。4种多态性在NTG患者和对照组之间的等位基因或基因型频率均无显著差异。在进一步比较有DH的NTG与正常对照组基因型频率的分析中，rs2070744的CC/CT基因型与NTG患者的DH显著相关（基因型关联检验，P值=0.0041）。在对性别和年龄等协变量进行校正的多元逻辑回归分析中，有DH的NTG与rs2070744的多态性基因型具有临界显著性（加性遗传模型，P=0.0070）。
我们的结果表明，eNOS rs2070744可能与有DH的NTG患者相关。这一发现提示，eNOS基因多态性可能是NTG患者发生DH的一个遗传危险因素。
