Department of Pulmonary Diseases, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey,
Mol Biol Rep. 2013 Oct;40(10):5625-33. doi: 10.1007/s11033-013-2664-6. Epub 2013 Sep 21.
Different biochemical pathways and cellular mechanisms play role in the pathogenesis of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). Alveolar hypoxia is not the only determinant of vascular remodeling, genetic factors are thought to have additive effects. We aimed to investigate the effects of endothelial nitric oxide synthase (eNOS A/B), angiotensin converting enzyme (ACE I/D) and serotonin transporter (5-HTT L/S) gene polymorphisms on development and severity of PH in COPD patients. 50 COPD patients without PH (group 1); 30 COPD patients with PH confirmed with echocardiography (group 2) and 49 healthy subjects (group 3) as control group were included to the study. eNOS A/B, ACE I/D and 5-HTT L/S gene polymorphisms and allele frequencies of COPD patients with and without PH and healthy subjects were determined. Functional parameters and echocardiographic measurements were recorded. Patients with PH were also assessed in two subgroups according to the severity of pulmonary arterial pressure (PAP). Significant differences among three groups in the distribution of 5-HTT genotype and allele frequency were present (respectively p = 0.002; p = 0.021). In group 2, LL and LS genotype rate was 93.3 % with a frequency of 71.2 % L allele and 28.3 % of S allele. 5-HTT LL genotype was present in 88.9 % of patients with PAP ≥50 mmHg significantly (p = 0.012). Other genotype distributions were not significantly different between two subgroups. The results of this study can suggest that COPD patients with L allele of 5-HTT may have higher risk for the development of PH and patients with LL genotype of 5-HTT may present higher PAP. We also demonstrated that eNOS and ACE gene polymorphisms were not associated with the development and severity of PH in our study population. Further studies with larger numbers of patients are needed to explore these relationships.
不同的生化途径和细胞机制在慢性阻塞性肺疾病（COPD）中的肺动脉高压（PH）发病机制中起作用。肺泡缺氧并不是血管重塑的唯一决定因素，遗传因素被认为具有附加作用。我们旨在研究内皮型一氧化氮合酶（eNOS A/B）、血管紧张素转换酶（ACE I/D）和 5-羟色胺转运体（5-HTT L/S）基因多态性对 COPD 患者 PH 的发展和严重程度的影响。50 名无 PH 的 COPD 患者（第 1 组）；30 名经超声心动图证实有 PH 的 COPD 患者（第 2 组）和 49 名健康受试者（第 3 组）作为对照组纳入研究。确定了 COPD 患者有无 PH 及健康受试者的 eNOS A/B、ACE I/D 和 5-HTT L/S 基因多态性和等位基因频率。记录了功能参数和超声心动图测量值。还根据肺动脉压（PAP）的严重程度将 PH 患者分为两个亚组进行评估。三组之间 5-HTT 基因型和等位基因频率的分布存在显著差异（分别为 p = 0.002；p = 0.021）。在第 2 组中，LL 和 LS 基因型的发生率为 93.3%，L 等位基因的频率为 71.2%，S 等位基因的频率为 28.3%。PAP≥50mmHg 的患者中存在 5-HTT LL 基因型，差异有统计学意义（p = 0.012）。两个亚组之间其他基因型的分布无显著差异。这项研究的结果表明，5-HTT 的 L 等位基因可能使 COPD 患者发生 PH 的风险更高，而 5-HTT 的 LL 基因型的患者可能存在更高的 PAP。我们还表明，在我们的研究人群中，eNOS 和 ACE 基因多态性与 PH 的发展和严重程度无关。需要进一步进行更大规模的患者研究来探索这些关系。
