Am. J. Respir. Crit. Care Med., Volume 160, Number 1, July 1999, 278-282

Prevalence of Tumor Necrosis Factor- and Angiotensin Converting Enzyme Polymorphisms in Mild/Moderate and Fatal/Near-Fatal Asthma

TABASSUM CHAGANI, PETER D. PARÉ, SHOUKANG ZHU, TRACEY D. WEIR, TONY R. BAI, NASSER A. BEHBEHANI, kJ. MARKk FITZGERALD, and ANDREW J. SANDFORD

University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada; Department of Medicine, Kuwait University, Safat, Kuwait; and Mater Miscordiae Hospital, Eccles Street, Dublin, Republic of Ireland

Allele 2 of the polymorphism at position 308 in the promoter of the tumor necrosis factor  (TNF-) gene, and the D allele of the angiotensin converting enzyme (ACE) gene, have been associated with asthma. We hypothesized that genotypes containing these alleles would show an increased prevalence in asthmatic as compared with nonasthmatic individuals, and would be associated with asthma severity. Polymerase chain reaction-based assays were developed to determine TNF- and ACE genotypes among subjects with mild/moderate asthma (n = 92), fatal/near-fatal asthma (n = 159), no asthma (n = 43), and random population controls (n = 252). The TNF- 308 polymorphism was increased in both subjects with mild/moderate (p = 0.03) and those with fatal/near fatal asthma (p = 0.02) versus those without asthma, and in all subjects with asthma versus random population controls (p = 0.02). The mild/moderate group was subdivided into subjects with mild (n = 43) and those with moderate (n = 33) asthma. TNF- 308 was increased in the moderately asthmatic versus the nonasthmatic subjects (p = 0.003), and in the mildly asthmatic subjects (p = 0.01). However, TNF- 308 was not significantly more prevalent in the fatal/near-fatal than in the mild/moderate asthmatic group. The ACE-D allele did not show an association with either asthma or asthma severity. We conclude that the TNF- 308 polymorphism may be a risk factor for asthma but does not increase the risk of a fatal or a near-fatal asthma attack, whereas the ACE polymorphism is not associated with asthma in this population.

This article has been cited by other articles:

				F. D. Finkelman, S. P. Hogan, G. K. K. Hershey, M. E. Rothenberg, and M. Wills-Karp Importance of Cytokines in Murine Allergic Airway Disease and Human Asthma J. Immunol., February 15, 2010; 184(4): 1663 - 1674. [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]

				M. Cardelli, L. Cavallone, F. Marchegiani, F. Oliveri, S. Dato, A. Montesanto, F. Lescai, R. Lisa, G. De Benedictis, and C. Franceschi A Genetic-Demographic Approach Reveals Male-Specific Association Between Survival and Tumor Necrosis Factor (A/G)-308 Polymorphism J Gerontol A Biol Sci Med Sci, May 1, 2008; 63(5): 454 - 460. [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]

				J Gao, G Shan, B Sun, P J Thompson, and X Gao Association between polymorphism of tumour necrosis factor {alpha}-308 gene promoter and asthma: a meta-analysis Thorax, June 1, 2006; 61(6): 466 - 471. [Abstract] [Full Text] [PDF]

				Y.-F. Li, W. J. Gauderman, E. Avol, L. Dubeau, and F. D. Gilliland Associations of Tumor Necrosis Factor G-308A with Childhood Asthma and Wheezing Am. J. Respir. Crit. Care Med., May 1, 2006; 173(9): 970 - 976. [Abstract] [Full Text] [PDF]

				H. Bilolikar, A. R. Nam, M. Rosenthal, J. C. Davies, D. C. Henderson, and I. M. Balfour-Lynn Tumour necrosis factor gene polymorphisms and childhood wheezing Eur. Respir. J., October 1, 2005; 26(4): 637 - 646. [Abstract] [Full Text] [PDF]

				A. G. Randolph, C. Lange, E. K. Silverman, R. Lazarus, and S. T. Weiss Extended Haplotype in the Tumor Necrosis Factor Gene Cluster Is Associated with Asthma and Asthma-related Phenotypes Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 687 - 692. [Abstract] [Full Text] [PDF]

				H. D. Shin, B. L. Park, L. H. Kim, J. H. Jung, H. J. Wang, Y. J. Kim, H.-S. Park, S.-J. Hong, B. W. Choi, D.-J. Kim, et al. Association of tumor necrosis factor polymorphisms with asthma and serum total IgE Hum. Mol. Genet., February 15, 2004; 13(4): 397 - 403. [Abstract] [Full Text] [PDF]

				E. R. McFadden Jr. Acute Severe Asthma Am. J. Respir. Crit. Care Med., October 1, 2003; 168(7): 740 - 759. [Abstract] [Full Text] [PDF]

				E. Noguchi, Y. Yokouchi, M. Shibasaki, M. Inudou, S. Nakahara, T. Nogami, M. Kamioka, K. Yamakawa-Kobayashi, K. Ichikawa, A. Matsui, et al. Association between TNFA Polymorphism and the Development of Asthma in the Japanese Population Am. J. Respir. Crit. Care Med., July 1, 2002; 166(1): 43 - 46. [Abstract] [Full Text] [PDF]

				W. O. C. Cookson Asthma Genetics Chest, March 1, 2002; 121 (2009): 7S - 13S. [Abstract] [Full Text] [PDF]

				I. PIN, V. SIROUX, C. CANS, F. KAUFFMANN, J. MACCARIO, C. PISON, and M.-H. DIZIER Familial Resemblance of Asthma Severity in the EGEA* Study Am. J. Respir. Crit. Care Med., January 15, 2002; 165(2): 185 - 189. [Abstract] [Full Text] [PDF]

				K G Tantisira and S T Weiss Complex interactions in complex traits: obesity and asthma Thorax, September 1, 2001; 56(90002): ii64 - 74. [Full Text] [PDF]

				A. J. SANDFORD, T. CHAGANI, T. D. WEIR, J. E. CONNETT, N. R. ANTHONISEN, and P. D. PARÉ Susceptibility Genes for Rapid Decline of Lung Function in the Lung Health Study Am. J. Respir. Crit. Care Med., February 1, 2001; 163(2): 469 - 473. [Abstract] [Full Text]

				W. O.C. Cookson and M. F. Moffatt Genetics of asthma and allergic disease Hum. Mol. Genet., October 1, 2000; 9(16): 2359 - 2364. [Abstract] [Full Text] [PDF]