Department of Thoracic Medicine, The Prince Charles Hospital, Rode Rd, Chermside, Brisbane, QLD 4032, Australia.
BMC Pulm Med. 2012 Jun 13;12:25. doi: 10.1186/1471-2466-12-25.
Pulmonary hypertension (PH) is a complication of chronic obstructive pulmonary disease (COPD). This study examined genetic variations in mediators of vascular remodelling and their association with PH in patients with COPD. In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia.
In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia.
580 COPD patients were recruited, 341 patients had a transthoracic echocardiogram, with RVSP measurable in 278 patients (mean age 69 years, mean FEV1 50% predicted, mean RVSP 44 mmHg, median history of 50 pack-years). Of the 7 tested SNPs, the NOS3-VNTR polymorphism was significantly associated with RVSP in a dose-dependent fashion for the risk allele: mean RVSP for a/a and a/b genotypes were 52.0 and 46.6 mmHg respectively, compared to 43.2 mmHg for b/b genotypes (P = 0.032). No associations were found between RVSP and other polymorphisms. ACE II or ID genotypes were associated with a lower FEV1% predicted than the ACE DD genotype (P = 0.028). The NOS3-298 TT genotype was associated with lower KCO % predicted than the NOS3-298 GG or GT genotype (P = 0.031).
The NOS3-VNTR polymorphism was associated with RVSP in patients with COPD, supporting its involvement in the pathogenesis of PH in COPD. ACE and NOS3 genotypes were associated with COPD disease severity, but not with the presence of PH. Further study of these genes could lead to the development of prognostic and screening tools for PH in COPD.
肺动脉高压（PH）是慢性阻塞性肺疾病（COPD）的并发症。本研究检测了血管重塑介质中的遗传变异及其与 COPD 患者 PH 的相关性。在 COPD 患者中，我们对 6 个候选 PH 基因（NOS3、ACE、EDN1、PTGIS、SLC6A4、VEGFA）中的 7 个 SNP 进行了基因分型。我们检测了与右心室收缩压（RVSP）、肺量计和气体转移以及低氧血症的相关性。
在 COPD 患者中，我们对 6 个候选 PH 基因（NOS3、ACE、EDN1、PTGIS、SLC6A4、VEGFA）中的 7 个 SNP 进行了基因分型。我们检测了与右心室收缩压（RVSP）、肺量计和气体转移以及低氧血症的相关性。
共纳入 580 例 COPD 患者，341 例行经胸超声心动图检查，278 例可测量 RVSP（平均年龄 69 岁，平均 FEV1 预测值 50%，平均 RVSP 44mmHg，中位吸烟史 50 包年）。在检测的 7 个 SNP 中，NOS3-VNTR 多态性与 RVSP 呈剂量依赖性相关，风险等位基因：a/a 和 a/b 基因型的平均 RVSP 分别为 52.0 和 46.6mmHg，而 b/b 基因型的平均 RVSP 为 43.2mmHg（P=0.032）。RVSP 与其他多态性之间无相关性。ACE II 或 ID 基因型与 ACE DD 基因型相比，FEV1%预测值较低（P=0.028）。NOS3-298 TT 基因型与 NOS3-298 GG 或 GT 基因型相比，KCO%预测值较低（P=0.031）。
NOS3-VNTR 多态性与 COPD 患者的 RVSP 相关，支持其参与 COPD 患者 PH 的发病机制。ACE 和 NOS3 基因型与 COPD 疾病严重程度相关，但与 PH 的存在无关。进一步研究这些基因可能会开发出 COPD 患者 PH 的预后和筛查工具。
