The transforming growth factor-beta1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD).
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.
Celedón
Juan C
JC
Channing Laboratory, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. juan.celedon@channing.harvard.edu
Lange
Christoph
C
Raby
Benjamin A
BA
Litonjua
Augusto A
AA
Palmer
Lyle J
LJ
DeMeo
Dawn L
DL
Reilly
John J
JJ
Kwiatkowski
David J
DJ
Chapman
Harold A
HA
Laird
Nan
N
Sylvia
Jody S
JS
Hernandez
Melvin
M
Speizer
Frank E
FE
Weiss
Scott T
ST
Silverman
Edwin K
EK
D016022:Case-Control Studies; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D005819:Genetic Markers; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1