This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 2006-0084OCv1 35/4/488    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sharma, S. Articles by Ghosh, B. Search for Related Content PubMed PubMed Citation Articles by Sharma, S. Articles by Ghosh, B.

Association of TNF Haplotypes with Asthma, Serum IgE Levels, and Correlation with Serum TNF- Levels

Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi; Department of Medicine, All India Institute of Medical Sciences, Delhi, India

Correspondence and requests for reprints should be addressed to Dr. Balaram Ghosh, Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India. E-mail: bghosh{at}igib.res.in

Both biochemical and genetic evidence have implicated the genes for TNF- (TNFA) and lymphotoxin- (LTA) in atopic asthma. Here, we report for the first time the association of their genotypes and haplotypes with atopic asthma in Indian populations. We genotyped seven single nucleotide polymorphisms, encompassing the two genes, in patients and control subjects in two independent cohorts. Serum TNF- levels of selected individuals were measured and correlated with genotypes and haplotypes. The A allele of the TNFA–863C > A polymorphism was associated with reduced risk of asthma (P = 0.002 and 0.007 in Cohorts A and B, respectively), reduced TsIgE levels (P = 0.0024 and P = 0.0029 in Cohorts A and B, respectively), and reduced serum TNF- levels (P < 0.05). A marginal association was also observed for LTA_NcoI polymorphism with asthma and TsIgE levels. Furthermore, analysis using HAPLO. STATS showed significant differences in the major haplotype frequencies (> 3%) between patients and control subjects (P = 0.002 and P = 0.006 for Cohorts A and B, respectively). Individually, the haplotype GATCCG was the most frequent in patients (P = 0.0029 and P = 0.0025 for Cohorts A and B, respectively), and was associated with high TsIgE and serum TNF- levels, whereas AACACG was the most frequent in the control subjects (P = 0.0032 and P = 0.022 for Cohorts A and B, respectively), and was associated with low TsIgE and serum TNF- levels. We also report here that the C > A substitution at position –863 of the TNFA influences the binding of nuclear proteins in electrophoretic mobility shift assay experiments. Thus, the TNFA–863C > A polymorphism in the promoter region of TNFA may influence TNF- expression and affect TsIgE levels and susceptibility to asthma.

Key Words: asthma • haplotype • Indian population • LTA • TNF-

This article has been cited by other articles:

				J. F. Alcorn, K. Ckless, A. L. Brown, A. S. Guala, J. K. Kolls, M. E. Poynter, C. G. Irvin, A. van der Vliet, and Y. M. W. Janssen-Heininger Strain-dependent activation of NF-{kappa}B in the airway epithelium and its role in allergic airway inflammation Am J Physiol Lung Cell Mol Physiol, January 1, 2010; 298(1): L57 - L66. [Abstract] [Full Text] [PDF]

				J. Kumar, G. Garg, A. Kumar, E. Sundaramoorthy, K. R. Sanapala, S. Ghosh, G. Karthikeyan, L. Ramakrishnan, Indian Genome Variation Consortium, and S. Sengupta Single Nucleotide Polymorphisms in Homocysteine Metabolism Pathway Genes: Association of CHDH A119C and MTHFR C677T With Hyperhomocysteinemia Circ Cardiovasc Genet, December 1, 2009; 2(6): 599 - 606. [Abstract] [Full Text] [PDF]

				A. L. Van Dyke, M. L. Cote, A. S. Wenzlaff, W. Chen, J. Abrams, S. Land, C. N. Giroux, and A. G. Schwartz Cytokine and Cytokine Receptor Single-Nucleotide Polymorphisms Predict Risk for Non-Small Cell Lung Cancer among Women Cancer Epidemiol. Biomarkers Prev., June 1, 2009; 18(6): 1829 - 1840. [Abstract] [Full Text] [PDF]

				R. Mahajan, E. M. El-Omar, J. Lissowska, P. Grillo, C. S. Rabkin, A. Baccarelli, M. Yeager, L. H. Sobin, W. Zatonski, S. J. Channock, et al. Genetic Variants in T Helper Cell Type 1, 2 and 3 Pathways and Gastric Cancer Risk in a Polish Population Jpn. J. Clin. Oncol., September 1, 2008; 38(9): 626 - 633. [Abstract] [Full Text] [PDF]

				F. Castro-Giner, M. Kogevinas, M. Machler, R. de Cid, K. Van Steen, M. Imboden, C. Schindler, W. Berger, J. R. Gonzalez, K. A. Franklin, et al. TNFA -308G>A in two international population-based cohorts and risk of asthma Eur. Respir. J., August 1, 2008; 32(2): 350 - 361. [Abstract] [Full Text] [PDF]

				V. B. Guzman, A. Yambartsev, A. Goncalves-Primo, I. D.C.G. Silva, C. R.N. Carvalho, J. C.L. Ribalta, L. R. Goulart, N. Shulzhenko, M. Gerbase-DeLima, and A. Morgun New approach reveals CD28 and IFNG gene interaction in the susceptibility to cervical cancer Hum. Mol. Genet., June 15, 2008; 17(12): 1838 - 1844. [Abstract] [Full Text] [PDF]

				K. L. McCann and F. Imani Transforming Growth Factor {beta} Enhances Respiratory Syncytial Virus Replication and Tumor Necrosis Factor Alpha Induction in Human Epithelial Cells J. Virol., March 15, 2007; 81(6): 2880 - 2886. [Abstract] [Full Text] [PDF]