Tumor necrosis factor--alpha and transforming growth factor--beta1 polymorphisms in bronchial asthma.
BACKGROUND
Bronchial asthma is a complex genetic disorder regulated by the release of cytokines and inflammatory mediators. Tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta1) cytokines play pivotal roles in the inflammatory response of the airways. Differential production of these two cytokines is associated with allelic variations in the transcriptional regulatory region of these genes.


OBJECTIVE
The objective of the present study was to investigate G-308A TNF-alpha and C-509T TGF- beta1 polymorphisms for their association with Bronchial Asthma.


METHODS
DNA isolated from 123 asthmatics and 100 normal healthy controls were screened for these polymorphisms using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) methods, developed in our laboratory.


RESULTS
Significant allelic association was observed between G-308A TNF-alpha polymorphism and asthma (P = 0.031) while no association was observed with C-509T TGF- beta1 polymorphism (P = 0.207). Further sub-grouping based on either allergic response or family history failed to reveal any statistical significance among the groups or with controls. The interaction between these polymorphisms revealed statistically significant association between the high producer genotype alleles of TNF-alpha and TGF-beta (A/T) and asthma (P = 0.016).


CONCLUSIONS
The present study reports, for the first time, the role of two polymorphisms, in concert, for their association with asthma in an Indian population. Our study supports the findings that the G-308A TNF-alpha promoter polymorphism is a risk factor for asthma and furthermore suggests that the patients with high producer alleles for TNF-alpha (-308) and TGF-beta (-509) have the highest risk of getting this disease in the Punjabi population.
Kumar
Ajay
A
Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, India.
Gupta
Vikas
V
Changotra
Harish
H
Sarin
B C
BC
Sehajpal
Prabodh K
PK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha