Transforming Growth Factor-β1Promoter Polymorphism C–509T Is Associated with Asthma

Eric S. Silverman, Lyle J. Palmer, Venkat Subramaniam, Arlene Hallock, Sheeba Mathew, Joseph Vallone, Debora S. Faffe, Toshiki Shikanai, Benjamin A. Raby, Scott T. Weiss, Stephanie A. Shore
2004 American Journal of Respiratory and Critical Care Medicine  
Transforming growth factor β1 (TGFB1) is increased in the lungs of asthmatics and may modulate airway inflammation and remodeling. Some genetic studies have found that a C to T single nucleotide polymorphism (C-509T) in the TGFB1 gene promoter may be associated with altered gene expression and asthma phenotype. To build on these data, we performed a casecontrol association study at this locus involving 527 asthmatics and 170 controls without asthma. All individuals were Caucasians. Genotyping
more » ... sians. Genotyping at 49 unlinked polymorphisms indicated that a subset of cases and all controls were well matched and without evidence of population stratification. Logistic regression was used to model the effects of age, gender, and genotype on case-control status. The diagnosis of asthma was positively associated with the T allele and TT genotype under a co-dominant model (OR = 2.98, 95% CI = 1.45 to 6.25, p =0.003). Total serum IgE, eosinophil count, and FEV 1 % predicted levels were not associated with this polymorphism. Furthermore, we show that the C-509T polymorphism alters TGFB1 promoterreporter activity and promoter interactions with the transcription factor Yin Yang 1. We conclude that the T allele of C-509T is associated with the diagnosis of asthma and may enhance TGFB1 gene transcription. Abstract Word Count: 199
doi:10.1164/rccm.200307-973oc pmid:14597484 fatcat:6yskty3q4jauhp3ugwfhuotmku