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. 2006 Nov 15;174(10):1101-9.
doi: 10.1164/rccm.200509-1405OC. Epub 2006 Aug 24.

Sequence, haplotype, and association analysis of ADRbeta2 in a multiethnic asthma case-control study

Gregory A Hawkins  1 , Kelan Tantisira, Deborah A Meyers, Elizabeth J Ampleford, Wendy C Moore, Barbara Klanderman, Stephen B Liggett, Stephen P Peters, Scott T Weiss, Eugene R Bleecker
Affiliations

Sequence, haplotype, and association analysis of ADRbeta2 in a multiethnic asthma case-control study

Gregory A Hawkins et al. Am J Respir Crit Care Med. .

Abstract

Rationale: The comprehensive evaluation of gene variation, haplotype structure, and linkage disequilibrium is important in understanding the function of beta2-adrenergic receptor gene (ADRbeta2) on disease susceptibility, pulmonary function, and therapeutic responses in different ethnic groups with asthma.

Objectives: To identify ADRbeta2 polymorphisms and haplotype structure in white and African American subjects and to test for genotype and haplotype association with asthma phenotypes.

Methods: A 5.3-kb region of ADRbeta2 was resequenced in 669 individuals from 429 whites and 240 African Americans. A total of 12 polymorphisms, representing an optimal haplotype tagging set, were genotyped in whites (338 patients and 326 control subjects) and African Americans (222 patients and 299 control subjects).

Results: A total of 49 polymorphisms were identified, 21 of which are novel; 31 polymorphisms (frequency > 0.03) were used to identify 24 haplotypes (frequency > 0.01) and assess linkage disequilibrium. Association with ratio (FEV1/FVC)2 for single-nucleotide polymorphism +79 (p < 0.05) was observed in African Americans. Significant haplotype association for (FEV1/FVC)2 was also observed in African Americans.

Conclusions: There are additional genetic variants besides +46 (Gly16Arg) that are important in determining asthma phenotypes. These data suggest that the length of a poly-C repeat (+1269) in the 3' untranslated region of ADRbeta2 may influence lung function, and may be important in delineating variation in beta-agonist responses, especially in African Americans.

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Figures

<b>Figure 1.</b>
Figure 1.
Position of polymorphisms in ADRβ2.
See this image and copyright information in PMC

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