RESUMEN
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. Aims: 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. Materials and 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.
RESUMEN
BACKGROUND: Tumour necrosis factor (TNF)-alpha is a pleiotropic, pro-inflammatory cytokine of 17 kDa, whose gene is localized on the short arm of chromosome 6. It has a G-308A polymorphism in the promoter region, which is known to be associated with its differential production; the A allele being the high producer. The circulating level of TNF-alpha is under genetic control and implicated in the pathophysiology of asthma and tuberculosis. Since raised levels of TNF-alpha have been found in asthma and tuberculosis, we looked for the association of TNF-alpha G-308A polymorphism in patients with these diseases. METHODS: A total of 300 blood samples from patients (155 with asthma, 145 tuberculosis) and 211 normal healthy controls were collected. The G-308A polymorphism was studied using amplification refractory mutation system analysis. RESULTS: The distribution of G/A alleles in the two patient groups when compared with normal controls revealed a statistically significant association with asthma (p = 0.016) but not with tuberculosis (p = 0.178). CONCLUSION: The data support the common variant common disease hypothesis, which emphasizes that common genetic variations may participate as critical players in inciting common diseases.