TGFβ1 haplotypes and asthma in Indian populations

Background: Asthma is a complex disorder of the airways of the lungs. TGF-β1 plays a key role in airway remodeling and asthma by having both proinflammatory and anti-inflammatory activities, making TGFβ1 an important candidate gene to study. Objective: To investigate the association of TGFβ1 gene polymorphisms with asthma. Methods: A case-control study was designed for identifying polymorphisms and haplotypes associated with asthma and associated phenotypes. We have verified our results in 2 independent cohorts collected from northern (number of patients, 187; number of controls, 187) and western India (number of patients, 209; number of controls, 190). We measured the serum TGF-β1 levels of selected individuals and correlated them with genotypes and haplotypes. Results: A novel (CT)n(CA)m repeat polymorphism (BV209662) 24.9 kb upstream of TGFβ1 was identified. A significant association was seen at the level of alleles and genotypes with asthma in the 2 cohorts studied independently (P < .05). Interestingly, a novel 3-locus haplotype, 23_G_T, was found to be significantly associated with asthma (P = .00001 in cohorts A and B) as well as with higher serum TGF-β1 level (P = .01). On the other hand, a novel haplotype, 22_G_C, was negatively associated with asthma (P = .00001 for cohorts A and B) and with lower serum TGF-β1 level (P = .0019). Conclusion: This is the first study identifying novel risk and protective haplotypes-23_G_T and 22_G_C, respectively-in the TGFβ1 gene that are associated with asthma. We also demonstrate the functional significance of these haplotypes with serum TGF-β1 levels. These results would be valuable in elucidating the role of TGF-β1 in asthma pathogenesis