Verde Zoraida, Santiago Catalina, Chicharro Luis M, Bandrés Fernando, Gómez-Gallego Félix, Rodríguez González-Moro Jose Miguel, de Lucas Pilar
Department of Biochemistry, Molecular Biology and Physiology, Universidad de Valladolid, Soria, Spain.
Department of Biomedical Sciences, Universidad Europea, Villaviciosa de Odón, Madrid, Spain.
Arch Bronconeumol (Engl Ed). 2019 Mar;55(3):128-133. doi: 10.1016/j.arbres.2018.07.021. Epub 2018 Sep 12.
Cigarette smoking is a major risk factor in the development of chronic obstructive pulmonary disease (COPD). Serotonin levels have been associated with COPD and smoking has been as a significant modulator. Elevated levels of serotonin are responsible for bronchoconstriction and pulmonary vasoconstriction and also nicotine dependence, thus serotonin response could be affected by genetic polymorphisms in transporters and receptors of serotonin.
The aim of the current study was to analyze the effect of SLC6A4 (5HTT_LPR) (rs25531) and HTR2A-1438G/A (rs6311) genetic polymorphisms on the relation between smoking habits and COPD.
The association between SLC6A4 (5HTT_LPR) (rs25531), HTR2A-1438G/A (rs6311), smoking degree and COPD was analyzed in a total of 77 COPD patients (active smokers) and 90 control subjects (active healthy smokers). The DNA was extracted of peripheral leukocytes samples and genotyping was performed using an allele specific polymerase chain reaction.
The distribution of SLC6A4 genotypes did not vary between healthy smokers and COPD patients (P=0.758). On the other hand, the A allele of HTR2A (rs6311) was significantly associated with COPD incidence in the trend model (P=0.02; 1.80 [1.04-3.11]). Among all smokers, this allele was also associated with the number of pack years smoked (P=0.02) and also, we observed a marginal association with FEV1/FVC values (P=0.06).
Our results point a possible role of the A allele of HTR2A (rs6311) in COPD pathogenesis, suggesting that this effect depends partly on tobacco consumption due to a gene-by-environment interaction.
吸烟是慢性阻塞性肺疾病（COPD）发展的主要危险因素。血清素水平与COPD相关，且吸烟是一个重要的调节因素。血清素水平升高会导致支气管收缩和肺血管收缩，同时也会导致尼古丁依赖，因此血清素反应可能会受到血清素转运体和受体基因多态性的影响。
本研究旨在分析SLC6A4（5HTT_LPR）（rs25531）和HTR2A - 1438G/A（rs6311）基因多态性对吸烟习惯与COPD之间关系的影响。
共分析了77例COPD患者（现吸烟者）和90例对照受试者（健康现吸烟者）中SLC6A4（5HTT_LPR）（rs25531）、HTR2A - 1438G/A（rs6311）、吸烟程度与COPD之间的关联。从外周血白细胞样本中提取DNA，并使用等位基因特异性聚合酶链反应进行基因分型。
健康吸烟者和COPD患者之间SLC6A4基因型的分布没有差异（P = 0.758）。另一方面，在趋势模型中，HTR2A（rs6311）的A等位基因与COPD发病率显著相关（P = 0.02；1.80 [1.04 - 3.11]）。在所有吸烟者中，该等位基因也与吸烟包年数相关（P = 0.02），并且，我们观察到与FEV1/FVC值存在边缘关联（P = 0.06）。
我们的结果表明HTR2A（rs6311）的A等位基因在COPD发病机制中可能起作用，提示这种效应部分取决于基因与环境的相互作用导致的烟草消费情况。
