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Intercellular adhesion molecule-1 and childhood asthma

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Abstract

We investigated the role of intercellular adhesion molecule-1 in childhood asthma by examining associations of functional variants at codons 29 (A→T), 241 (G→A), and 469 (A→G) in Children’s Health Study participants. Among African-Americans, 469G carriers had lower risk for asthma (ever asthma OR=0.4, 95% CI 0.2–0.9) but increased risk among 29T carriers (early onset active asthma OR=2.2, 95% CI 1.0–4.9). Protective associations with the 241A allele were observed among non-Hispanic and Hispanic whites (ever asthma OR=0.7, 95% CI 0.6–0.9; early onset active asthma OR=0.5, 95% CI 0.4–0.8), and these associations were not confounded by population stratification. To gauge the potential impact of confounding by population stratification, we performed analyses by ethnic group and in an independent family-based sample. Regional associations were stable across analyses. Haplotype associations of the four common haplotypes (29A/241G/469A, AGG, TGA, and AAG) with asthma showed that Hispanics with the AAG haplotype had lower asthma risk compared to carriers of two copies of AGA haplotype (OR=0.6, 95% CI 0.4–0.9). Among non-Hispanic whites, the AAG haplotype was associated with reduced risk for active asthma. For African-Americans, who had a low frequency of the AAG haplotype, carrying one copy of the AGG haplotype was associated with a lower risk of asthma (OR=0.3, 95% CI 0.1–0.8), as compared with two copies of the AGA haplotype. Consistent with information on variant function, the 241A and 469G variants may indicate haplotypes that are associated with reduced risk for asthma.

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Acknowledgements

The authors thank the entire Children’s Health Study staff and study participants. This study was supported by the National Institute of Environmental Health Sciences (Grants: 1P01 ES09581, 5P01 ES11627 and 5P30 ES07048), the US Environmental Protection Agency (Grant R826708-01), the National Heart, Lung, Blood Institute (Grant 1R01HL61768), the California Air Resources Board (Contract 94-331), and the Hastings Foundation.

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Authors and Affiliations

  1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1540 Alcazar Street, CHP 236, Los Angeles, CA, 90033, USA

    Yu-Fen Li, Yo-Hsuang Tsao, W. James Gauderman, David V. Conti, Edward Avol & Frank D. Gilliland

  2. Department of Pathology, Keck School of Medicine, University of Southern California, 1540 Alcazar Street, CHP 236, Los Angeles, CA, 90033, USA

    Louis Dubeau

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  1. Yu-Fen Li
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  2. Yo-Hsuang Tsao
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  3. W. James Gauderman
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  4. David V. Conti
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  5. Edward Avol
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  6. Louis Dubeau
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  7. Frank D. Gilliland
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Correspondence to Frank D. Gilliland.

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Li, YF., Tsao, YH., Gauderman, W.J. et al. Intercellular adhesion molecule-1 and childhood asthma. Hum Genet 117, 476–484 (2005). https://doi.org/10.1007/s00439-005-1319-7

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