Intercellular adhesion molecule-1 and childhood asthma
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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.
KeywordsAsthma Airway Inflammation 469G Allele Lifetime Diagnosis Active Asthma
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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