Transforming growth factor-β1 genotype and susceptibility to chronic obstructive pulmonary disease
Transforming growth factor-β1 genotype and susceptibility to chronic obstructive pulmonary disease
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DOI：
10.1136/thorax.2003.005769
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发表时间：
2004-02-01
期刊：
影响因子：
10
通讯作者：
Black, PN
中科院分区：
文献类型：
--
作者：
Wu, L;Chau, J;Black, PN
背景资料：只有少数长期吸烟者会出现症状性慢性阻塞性肺疾病（COPD），这可能至少部分是由于对疾病的遗传易感性。转化生长因子β（1）（TGF-β（1））具有许多作用，使其成为COPD发病机制中的候选者。我们研究了TGF-β 1基因外显子1核苷酸位置29（T->C）的单核苷酸多态性，该多态性导致密码子10发生置换方法：在165名COPD患者，140名健康献血员，76名肺功能正常的吸烟者（耐药吸烟者）使用聚合酶链反应和限制性内切酶片段长度多态性。结果：基因型分布为Leu-Leu（41.8%），Leu-Pro（50.3%）和Pro-Pro COPD组为7.9%，与对照组相比差异有统计学意义（献血者：Leu-Leu（29.3%）、Leu-Pro（52.1%）和Pro-Pro（18.6%），p = 0.006;耐药吸烟者：Leu-Leu（28.9%）、Leu-Pro（51.3%）和Pro-Pro（19.7%），p = 0.02）。Pro（10）等位基因在COPD受试者中（33%）比献血者中更不常见（45%; OR = 0.62，95% CI 0.45至0.86，p = 0.005）和耐药吸烟者结论：TGF-β 1基因第10密码子的脯氨酸等位基因在对照组中比在COPD患者中更常见。该等位基因与TGF-β（1）的产生增加相关，这增加了TGF-β（1）在COPD中具有保护作用的可能性。
Background: Only a few long term smokers develop symptomatic chronic obstructive pulmonary disease (COPD) and this may be due, at least in part, to genetic susceptibility to the disease. Transforming growth factor beta(1) (TGF-beta(1)) has a number of actions that make it a candidate for a role in the pathogenesis of COPD. We have investigated a single nucleotide polymorphism at exon 1 nucleotide position 29 (T-->C) of the TGF-beta(1) gene that produces a substitution at codon 10 (Leu-->Pro).Methods: The frequency of this polymorphism was determined in 165 subjects with COPD, 140 healthy blood donors, and 76 smokers with normal lung function (resistant smokers) using the polymerase chain reaction and restriction enzyme fragment length polymorphism.Results: The distribution of genotypes was Leu-Leu (41.8%), Leu-Pro (50.3%), and Pro-Pro (7.9%) for subjects with COPD, which was significantly different from the control subjects (blood donors: Leu-Leu (29.3%), Leu-Pro (52.1%) and Pro-Pro (18.6%), p = 0.006; resistant smokers: Leu-Leu (28.9%), Leu-Pro (51.3%) and Pro-Pro (19.7%), p = 0.02). The Pro(10) allele was less common in subjects with COPD (33%) than in blood donors (45%; OR = 0.62, 95% CI 0.45 to 0.86, p = 0.005) and resistant smokers (45%; OR = 0.59, 95% CI 0.40 to 0.88, p = 0.01).Conclusions: The proline allele at codon 10 of the TGF-beta(1) gene occurs more commonly in control subjects than in individuals with COPD. This allele is associated with increased production of TGF-beta(1) which raises the possibility that TGF-beta(1) has a protective role in COPD.