TGFbeta1 haplotypes and asthma in Indian populations.
BACKGROUND
Asthma is a complex disorder of the airways of the lungs. TGF-beta1 plays a key role in airway remodeling and asthma by having both proinflammatory and anti-inflammatory activities, making TGFbeta1 an important candidate gene to study.


OBJECTIVE
To investigate the association of TGFbeta1 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-beta1 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 TGFbeta1 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-beta1 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-beta1 level (P = .0019).


CONCLUSIONS
This is the first study identifying novel risk and protective haplotypes--23_G_T and 22_G_C, respectively--in the TGFbeta1 gene that are associated with asthma. We also demonstrate the functional significance of these haplotypes with serum TGF-beta1 levels. These results would be valuable in elucidating the role of TGF-beta1 in asthma pathogenesis.
Nagpal
Kamalpreet
K
Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi, India.
Sharma
Shilpy
S
B-Rao
Chandrika
C
Nahid
Sanober
S
Niphadkar
Pramod V
PV
Sharma
Surendra K
SK
Ghosh
Balaram
B
D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000235:genetics* / Q000276:immunology
D016212:Transforming Growth Factor beta