Yi Kang, Guo Tao, Wang Wen-Xin, He Shao-E, Zhang Xin, Xu Jian-Guo, Wang Zi-Qiang, Wang Fan-Ning, You Tao
Department of Cardiovascular Surgery, Gansu Provincial Hospital, Lanzhou, China; Gansu International Scientific and Technological Cooperation Base of Diagnosis and Treatment of Congenital Heart Disease, Lanzhou, China.
Department of Cardiovascular Surgery, Gansu Provincial Hospital, Lanzhou, China; Gansu International Scientific and Technological Cooperation Base of Diagnosis and Treatment of Congenital Heart Disease, Lanzhou, China; The First School of Clinical Medicine of Gansu University of Chinese Medicine, Lanzhou, China.
Nitric Oxide. 2025 Feb;154:51-76. doi: 10.1016/j.niox.2024.11.009. Epub 2024 Nov 22.
We performed the present study to better elucidate the correlation of nitric oxide synthase 3 (NOS3) gene polymorphism with the risk of pulmonary arterial hypertension (PAH).
MATERIAL/METHODS: According to the designed search strategy, a systematic literature search was performed through the PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and Wan Fang databases to collect published case-control studies on the correlation between NOS3 gene polymorphism and PAH. The search deadline was December 26, 2023. Two reviewers independently screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. The odds ratio (OR) and 95 % confidence interval (CI) of the genotype distribution were used as the effect indicators.
A total of 11 eligible studies were included, involving three single nucleotide polymorphism (SNP) sites of the NOS3 gene: G894T (rs1799983), 4b/4a (rs61722009), and T-786C (rs2070744). The meta-analysis revealed that for PAH analysis, 4 genetic models of NOS3 G894T polymorphism increased the risk of PAH: the allele model (T vs G, OR = 1.9, 95%CI [1.16, 3.11],P = 0.01), the homozygote model (GG vs TT, OR = 1.91, 95%CI [1.04, 3.51], P = 0.04), the heterozygote model (GG vs GT, OR = 3.19, 95%CI [1.65, 6.19], P = 0.0006) and the dominant model (GT + TT vs GG, OR = 3.06, 95%CI [1.54, 6.09], P = 0.001). In the subgroups analysis, the NOS3 G894T polymorphism was found to be associated with the risk of PAH subgroups, including CHD combined with PAH and COPD combined with PAH, Particularly, there is a highly significant correlation with CHD combined with PAH. 2 genetic models of NOS3 4b/4a polymorphism increased the risk of PAH: the homozygote model (BB vs AA, OR = 2.1, 95%CI [1.02, 4.35], P = 0.04) and the recessive model (BB + BA vs AA, OR = 2.55, 95%CI [1.27, 5.11], P = 0.009). In the subgroups analysis, the NOS3 4b/4a polymorphism was found to be associated with the susceptibility of CHD combined with PAH. The results of the combined analysis of each gene model of NOS3 T-786C gene polymorphism sites were not statistically significant, and their P values were all>0.05. The NOS3 G894T and NOS3 4b/4a gene polymorphism had been found to be associated with the risk of PAH in different regional and racial subgroups. In contrast to the NOS3 G894T gene polymorphism, which increased the risk of PAH development in the yellow race subgroup, the NOS3 4b/4a gene polymorphism reduced the risk of PAH development in the white race subgroup and was a protective factor.
The NOS3 G894T (rs1799983) and NOS3 4b/4a (rs61722009) gene polymorphism have a strong correlation with the risk of PAH, with this association varying among different regions and ethnicities. However, it is still necessary to expand the sample size and conduct further studies to confirm whether the NOS3 T-786C (rs2070744) polymorphism tends to increase the incidence of PAH.
我们开展本研究以更好地阐明一氧化氮合酶3（NOS3）基因多态性与肺动脉高压（PAH）风险的相关性。
材料/方法：根据设计的检索策略，通过PubMed、Embase、Web of Science、Cochrane图书馆、中国知网、维普和万方数据库进行系统文献检索，以收集已发表的关于NOS3基因多态性与PAH相关性的病例对照研究。检索截止日期为2023年12月26日。两名研究者根据纳入和排除标准独立筛选文献、提取数据并评估质量。使用RevMan 5.4软件进行Meta分析。基因型分布的比值比（OR）和95%置信区间（CI）用作效应指标。
共纳入11项符合条件的研究，涉及NOS3基因的3个单核苷酸多态性（SNP）位点：G894T（rs1799983）、4b/4a（rs61722009）和T - 786C（rs2070744）。Meta分析显示，对于PAH分析，NOS3 G894T多态性的4种遗传模型增加了PAH风险：等位基因模型（T vs G，OR = 1.9，95%CI [1.16, 3.11]，P = 0.01）、纯合子模型（GG vs TT，OR = 1.91，95%CI [1.04, 3.51]，P = 0.
