Influence of C-159T SNP of the CD14 gene promoter on lung function in smokers.
Influence of C-159T SNP of the CD14 gene promoter on lung function in smokers.
复制标题
CD14基因启动子的C-159T SNP对吸烟者肺功能的影响。
DOI：
10.1016/j.rmed.2009.03.007
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发表时间：
2009
影响因子：
4.3
通讯作者：
Peden,DavidB
中科院分区：
文献类型：
--
作者：
Zhou,Haibo;Alexis,NeilE;Almond,Martha;Donohue,James;LaForce,Craig;Bromberg,PhilipA;Peden,DavidB
CD 14是内毒素的共受体，在调节对该试剂的炎症反应中起重要作用。CD 14基因启动子中的C-159 T单核苷酸多态性（SNP）是CD 14表达的重要调节因子，TT纯合子具有增加的CD 14表达。这种SNP与哮喘的发病机制和吸烟者的心血管疾病有关。我们推测，CD 14也在吸烟者的COPD病理生理学中发挥作用，吸烟者暴露于香烟烟雾中含有的内毒素以及来自革兰氏阴性微生物定植在其气道中的内毒素。为了评估CD 14基因启动子的C-159 T SNP对肺功能的影响，我们招募了246名40岁或以上的吸烟者，吸烟暴露范围为10-156包-年。TT基因型与中度吸烟史的吸烟者肺功能降低相关。然而，CC基因型与重度吸烟者（>56包年）的肺功能下降相关。CC基因型对COPD严重程度的影响与该基因型对哮喘风险的影响类似。CD 14可能是COPD病理生理学中的一个因素，就像它在哮喘和吸烟相关的心血管疾病中一样。
CD14, a co-receptor for endotoxin, plays a significant role in regulating the inflammatory response to this agent. The C-159T single nucleotide polymorphism (SNP) in the CD14 gene promoter is an important regulator of CD14 expression, with TT homozygotes having increased expression of CD14. This SNP has been linked to pathogenesis of asthma and with cardiovascular diseases in smokers. We hypothesize that CD14 also plays a role in the pathophysiology of COPD in smokers who are exposed to endotoxin contained in cigarette smoke as well as endotoxin derived from Gram-negative microbes colonizing their airways. To assess the effect of the C-159T SNP of the CD14 gene promoter on lung function, we recruited 246 smokers 40 years of age or older with a range of 10–156 pack-year smoking exposures. The TT genotype was associated with lower lung function in smokers with a moderate smoking history. However, the CC genotype was associated with decreased lung function in heavy smokers (>56 pack years). The effect of CC genotype on severity of COPD is analogous with the effect of this genotype in risk for asthma. CD14 may be a factor in the pathophysiology of COPD, as it is in asthma and smoking-related cardiovascular diseases.