The transforming growth factor-beta1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD).
The transforming growth factor-beta1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD).
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发表时间：
2004
影响因子：
3.5
通讯作者：
J. Celedón;C. Lange;B. Raby;A. Litonjua;L. Palmer;D. Demeo;J. Reilly;D. Kwiatkowski;H. Chapman;N. Laird;J. Sylvia;M. Hernandez;F. Speizer;S. Weiss;E. Silverman
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作者：
J. Celedón;C. Lange;B. Raby;A. Litonjua;L. Palmer;D. Demeo;J. Reilly;D. Kwiatkowski;H. Chapman;N. Laird;J. Sylvia;M. Hernandez;F. Speizer;S. Weiss;E. Silverman
虽然吸烟是主要的环境危险因素，但遗传危险因素可能会影响慢性阻塞性肺疾病(COPD)的发展。在19号染色体短串联重复序列标记与COPD表型之间的连锁分析之后，对19q染色体上的一个基因[转化生长因子-β1(TGFB1)]的单核苷酸多态性与COPD表型进行关联分析，并进行病例对照研究(重度COPD患者和有明显吸烟史但无COPD的对照组)。按吸烟状况分层显著改善了COPD表型与染色体19q连锁的证据。在波士顿早发性COPD研究中，在既往和现在的吸烟者中，有显著证据表明19q染色体与前支气管扩张(Pre-BD)FEV(1)(LOD=3.30)之间存在关联，并暗示19q染色体与其他COPD表型之间存在关联。在这些家系中，TGFB1启动子区域的一个SNP(Rs2241712)和TGFB1 3‘基因组区域的两个SNP(rs2241718和rs6957)与BD前、后FEV(1)显著相关(P<；0.05)。在COPD患者和对照组吸烟者中，TGFB1启动子区域的两个SNP(rs2241712和rs1800469)和TGFB1外显子1的一个SNP(Rs1982073)与COPD显著相关(P<0.05)。染色体19q可能包含一个(或多个)遗传基因座，该基因座通过与吸烟的相互作用影响COPD。我们假设TGFB1基因中或其附近的遗传变异影响吸烟人群中COPD的发病。
Although cigarette smoking is the primary environmental risk factor, genetic risk factors likely influence the development of chronic obstructive pulmonary disease (COPD). Linkage analysis between short-tandem repeat markers on chromosome 19 and COPD phenotypes was followed by association analysis of single nucleotide polymorphisms in a gene on chromosome 19q [transforming growth factor-beta1 (TGFB1)] and COPD phenotypes in a family-based sample and a case-control study (cases with severe COPD and control subjects with significant history of smoking but no COPD). Stratification by smoking status substantially improved the evidence of linkage to chromosome 19q for COPD phenotypes. Among former and current smokers in the Boston Early-Onset COPD Study, there was significant evidence of linkage between chromosome 19q and pre-bronchodilator (pre-BD) FEV(1) (LOD=3.30) and suggestive evidence of linkage between chromosome 19q and other COPD phenotypes. In these families, a SNP in the promoter region of TGFB1 (rs2241712) and two SNPs in the 3' genomic region of TGFB1 (rs2241718 and rs6957) were significantly associated with pre- and post-BD FEV(1) (P<0.05). Among smokers in the COPD cases and control subjects, two SNPs in the promoter region of TGFB1 (rs2241712 and rs1800469) and one SNP in exon 1 of TGFB1 (rs1982073) were significantly associated with COPD (P</=0.02 in all cases). Chromosome 19q likely contains a genetic locus (or loci) that influences COPD through an interaction with cigarette smoking. We hypothesize that genetic variants in or near the TGFB1 gene influence the pathogenesis of COPD among cigarette smokers.