Genetic Polymorphisms of the Serotonin Transporter, but Not the 2a Receptor or Nitric Oxide Synthetase, Are Associated with Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease
Genetic Polymorphisms of the Serotonin Transporter, but Not the 2a Receptor or Nitric Oxide Synthetase, Are Associated with Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease
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DOI：
10.1159/000226243
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发表时间：
2010-01-01
期刊：
影响因子：
3.7
通讯作者：
Speich, Rudolf
中科院分区：
文献类型：
--
作者：
Ulrich, Silvia;Hersberger, Martin;Speich, Rudolf
背景：肺动脉高压（PH）在慢性阻塞性肺疾病（COPD）中具有重要的预后意义。由于PH值与低氧血症的相关性较弱，因此一定有其他因素在起作用。目的：探讨慢性阻塞性肺疾病患者血清素转运体（5HTT）、血清素-2a受体（5HTR2a）和内皮型一氧化氮合成酶（eNOS）多态性是否与PH有关。方法：对59例经右心导管治疗的COPD患者进行6分钟步行距离、NYHA功能分级、肺功能检查、血气及5HTT、5HTR2a和eNOS （4ab和T298C）多态性检测。结果：纳入49例COPD患者，NYHA功能分级为III-IV级。10例因PH合并症（主要是慢性血栓栓塞）而被排除。55%的患者存在PH值（mPAP >= 25 mm Hg），通常为轻度，但12%的患者比例失调（mPAP >= 40 mm Hg）。PH患者的5htt - l等位基因频率（52%）明显高于非PH个体（36%），LL纯合子患者的PH更严重。在不成比例的PH患者中，l等位基因频率甚至达到75%。我们没有发现5HTR2a和eNOS多态性与COPD患者的PH值相关。结论：在这个COPD队列中，我们确认PH是频繁且通常是轻度的，但在一个亚组中比例过高。我们发现，5HTT的l等位基因变异与总体PH值，尤其是非比例PH值存在显著关联。这些发现可能指向5 -羟色胺系统在COPD-PH中的作用，值得进一步研究。版权所有(C) 2009 S. Karger AG，巴塞尔
Background: Pulmonary hypertension (PH) is prognostically important in chronic obstructive pulmonary disease (COPD). Since PH only weakly correlates with hypoxemia, other factors must play a role. Objective: To investigate whether polymorphisms of the serotonin transporter (5HTT), serotonin-2a receptor (5HTR2a) and endothelial nitric oxide synthetase (eNOS) are related to PH in COPD. Methods: In 59 COPD patients who underwent right heart catheterization, 6-min walking distance, NYHA functional class, pulmonary function tests, blood gases and 5HTT, 5HTR2a and eNOS (4ab and T298C) polymorphisms were determined. Results: Forty-nine COPD patients in NYHA functional class III-IV were included. Ten were excluded due to comorbid causes of PH (mainly chronic thromboembolic). PH (mPAP >= 25 mm Hg) was present in 55% and usually mild, but out of proportion (mPAP >= 40 mm Hg) in 12%. Patients with PH had significantly higher frequencies of the 5HTT-L-allele (52%) compared to individuals without PH (36%), and LL homozygote patients had more severe PH. In patients with out-of-proportion PH, the L-allelic frequency was even 75%. We found no association of 5HTR2a and eNOS polymorphism with PH in COPD. Conclusions: In this COPD cohort we confirm that PH is frequent and usually mild, but out of proportion in a subgroup. We found a significant association of the L-allelic variant of 5HTT with PH overall and especially in out-of-proportion PH. These findings may point towards a role of the serotonin system in COPD-PH and warrant further studies. Copyright (C) 2009 S. Karger AG, Basel