Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Wanyuan Road 399, Minhang District, Shanghai, 201102, China.
Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhengzhou, 450052, China.
BMC Med Genomics. 2018 Jun 25;11(1):56. doi: 10.1186/s12920-018-0374-6.
Cerebral palsy (CP) is the leading cause of motor disability in children; however, its pathogenesis is unknown in most cases. Growing evidence suggests that Nitric oxide synthase 1 (NOS1) is involved in neural development and neurologic diseases. The purpose of this study was to determine whether genetic variants of NOS1 contribute to CP susceptibility in a Han Chinese population.
A case-control study involving 652 CP patients and 636 healthy controls was conducted. Six SNPs in the NOS1 gene (rs3782219, rs6490121, rs2293054, rs10774909, rs3741475, and rs2682826) were selected, and the MassARRAY typing technique was applied for genotyping. Data analysis was conducted using SHEsis online software, and multiple test corrections were performed using SNPSpD online software.
There were no significant differences in genotype and allele frequencies between patients and controls for the SNPs except rs6490121, which deviated from Hardy-Weinberg equilibrium and was excluded from further analyses. Subgroup analysis revealed differences in genotype frequencies between the CP with neonatal encephalopathy group (CP + NE) and control group for rs10774909, rs3741475, and rs2682826 (after SNPSpD correction, p = 0.004, 0.012, and 0.002, respectively). The T allele of NOS1 SNP rs3782219 was negatively associated with spastic quadriplegia (OR = 0.742, 95% CI = 0.600-0.918, after SNPSpD correction, p = 0.023). There were no differences in allele or genotype frequencies between CP subgroups and controls for the other genetic polymorphisms.
NOS1 is associated with CP + NE and spastic quadriplegia, suggesting that NOS1 is likely involved in the pathogenesis of CP and that it is a potential therapeutic target for treatment of cerebral injury.
脑瘫（CP）是儿童运动障碍的主要原因；然而，在大多数情况下，其发病机制尚不清楚。越来越多的证据表明，一氧化氮合酶 1（NOS1）参与神经发育和神经疾病。本研究的目的是确定汉族人群中 NOS1 的遗传变异是否与 CP 易感性有关。
进行了一项病例对照研究，纳入 652 例 CP 患者和 636 名健康对照者。选择 NOS1 基因中的 6 个单核苷酸多态性（rs3782219、rs6490121、rs2293054、rs10774909、rs3741475 和 rs2682826），并应用 MassARRAY 基因分型技术进行基因分型。使用 SHEsis 在线软件进行数据分析，并使用 SNPSpD 在线软件进行多重检验校正。
除 rs6490121 外，患者和对照组之间的 SNP 基因型和等位基因频率均无显著差异，rs6490121 不符合 Hardy-Weinberg 平衡，因此被排除在进一步分析之外。亚组分析显示，CP 伴新生儿脑病组（CP+NE）与对照组之间的 rs10774909、rs3741475 和 rs2682826 基因型频率存在差异（经 SNPSpD 校正后，p 值分别为 0.004、0.012 和 0.002）。NOS1 SNP rs3782219 的 T 等位基因与痉挛性四肢瘫呈负相关（OR=0.742，95%CI=0.600-0.918，经 SNPSpD 校正后，p=0.023）。CP 各亚组与对照组之间的其他遗传多态性的等位基因或基因型频率无差异。
NOS1 与 CP+NE 和痉挛性四肢瘫有关，提示 NOS1 可能参与 CP 的发病机制，是治疗脑损伤的潜在治疗靶点。
