Am. J. Respir. Crit. Care Med., Volume 164, Number 11, December 2001, 2036-2044

Allelic Frequencies and Patterns of Single-nucleotide Polymorphisms in Candidate Genes for Asthma and Atopy in Iceland

HAKON HAKONARSON, UNNUR S. BJORNSDOTTIR, ELINBORG OSTERMANN, THOR ARNASON, ASDIS E. ADALSTEINSDOTTIR, EVA HALAPI, DANA SHKOLNY, KRISTLEIFUR KRISTJANSSON, SIGURBJORG A. GUDNADOTTIR, MICHAEL L. FRIGGE, DAVID GISLASON, THORARINN GISLASON, AUGUSTINE KONG, JEFFREY GULCHER, and KARI STEFANSSON

deCODE Genetics, Inc., and Vifilstadir University Hospital, Reykjavik, Iceland

Numerous asthma and atopy loci have been reported in studies demonstrating associations of the asthma-related phenotypes atopy, elevated IgE levels, and bronchial hyperresponsiveness with alleles of microsatellite markers and single-nucleotide polymorphisms (SNPs) within specific cytokine/chemokine and IgE-regulating genes. Although the studies reporting these observations are compelling, most of them lack statistical power. We assessed the nature, pattern, and frequency of SNPs in 24 candidate genes in Iceland and looked for associations with asthma and atopy. We identified 42 SNPs with an average minor allele frequency of 20.3% (asthma) and 20.7% (control). Twenty SNPs (48%) were within coding sequences and 90% of those led to a predicted change in protein sequence. No differences were detected in the allelic frequencies of SNPs in any of these candidate genes between control subjects and the patients with atopic asthma. Moreover, linkage analysis that included 269 patients with atopic asthma uncovered no evidence of linkage to markers associated with these genes. We conclude that this study has failed to produce evidence in support of the notion that variations within these 24 candidate atopy and asthma genes significantly influence the expression of the atopic asthmatic phenotype or contribute to the susceptibility of atopic asthma.

This article has been cited by other articles:

				A. J. Rogers, B. A. Raby, J. A. Lasky-Su, A. Murphy, R. Lazarus, B. J. Klanderman, J. S. Sylvia, J. P. Ziniti, C. Lange, J. C. Celedon, et al. Assessing the Reproducibility of Asthma Candidate Gene Associations, Using Genome-wide Data Am. J. Respir. Crit. Care Med., June 15, 2009; 179(12): 1084 - 1090. [Abstract] [Full Text] [PDF]

				S. Sharma, B. A. Raby, G. M. Hunninghake, M. Soto-Quiros, L. Avila, A. J. Murphy, J. Lasky-Su, B. J. Klanderman, J. S. Sylvia, S. T. Weiss, et al. Variants in TGFB1, Dust Mite Exposure, and Disease Severity in Children with Asthma Am. J. Respir. Crit. Care Med., March 1, 2009; 179(5): 356 - 362. [Abstract] [Full Text] [PDF]

				D. A. Schwartz Gene-Environment Interactions and Airway Disease in Children Pediatrics, March 1, 2009; 123(Supplement_3): S151 - S159. [Abstract] [Full Text] [PDF]

				X. Hong, H. Zhou, H-J. Tsai, X. Wang, X. Liu, B. Wang, X. Xu, and X. Xu Cysteinyl leukotriene receptor 1 gene variation and risk of asthma Eur. Respir. J., January 1, 2009; 33(1): 42 - 48. [Abstract] [Full Text] [PDF]

				M. J. Holtzman, J. W. Tyner, E. Y. Kim, M. S. Lo, A. C. Patel, L. P. Shornick, E. Agapov, and Y. Zhang Acute and Chronic Airway Responses to Viral Infection: Implications for Asthma and Chronic Obstructive Pulmonary Disease Proceedings of the ATS, August 1, 2005; 2(2): 132 - 140. [Abstract] [Full Text] [PDF]

				A. Thakkinstian, M. McEvoy, C. Minelli, P. Gibson, B. Hancox, D. Duffy, J. Thompson, I. Hall, J. Kaufman, T.-f. Leung, et al. Systematic Review and Meta-Analysis of the Association between {beta}2-Adrenoceptor Polymorphisms and Asthma: A HuGE Review Am. J. Epidemiol., August 1, 2005; 162(3): 201 - 211. [Abstract] [Full Text] [PDF]

				M-A Kedda, F Lose, D Duffy, E Bell, P J Thompson, and J Upham The CD14 C-159T polymorphism is not associated with asthma or asthma severity in an Australian adult population Thorax, March 1, 2005; 60(3): 211 - 214. [Abstract] [Full Text] [PDF]

				J. C. Celedon, C. Lange, B. A. Raby, A. A. Litonjua, L. J. Palmer, D. L. DeMeo, J. J. Reilly, D. J. Kwiatkowski, H. A. Chapman, N. Laird, et al. The transforming growth factor-{beta}1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD) Hum. Mol. Genet., August 1, 2004; 13(15): 1649 - 1656. [Abstract] [Full Text] [PDF]

				E. S. Silverman, L. J. Palmer, V. Subramaniam, A. Hallock, S. Mathew, J. Vallone, D. S. Faffe, T. Shikanai, B. A. Raby, S. T. Weiss, et al. Transforming Growth Factor-{beta}1 Promoter Polymorphism C-509T Is Associated with Asthma Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 214 - 219. [Abstract] [Full Text] [PDF]

				M. J. Holtzman Drug Development for Asthma Am. J. Respir. Cell Mol. Biol., August 1, 2003; 29(2): 163 - 171. [Abstract] [Full Text] [PDF]

				B. A. Raby, W. T. Klimecki, C. Laprise, Y. Renaud, J. Faith, M. Lemire, C. Greenwood, K. M. Weiland, C. Lange, L. J. Palmer, et al. Polymorphisms in Toll-Like Receptor 4 Are Not Associated with Asthma or Atopy-related Phenotypes Am. J. Respir. Crit. Care Med., December 1, 2002; 166(11): 1449 - 1456. [Abstract] [Full Text] [PDF]

				M. J. TOBIN Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2001 Am. J. Respir. Crit. Care Med., March 1, 2002; 165(5): 598 - 618. [Full Text] [PDF]

				S. T. Weiss Association Studies in Asthma Genetics Am. J. Respir. Crit. Care Med., December 1, 2001; 164(11): 2014 - 2015. [Full Text] [PDF]