Sequence, haplotype, and association analysis of ADRβ2 in a multiethnic asthma case-control study

Gregory A. Hawkins, 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

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

Rationale: The comprehensive evaluation of gene variation, haplotype structure, and linkage disequilibrium is important in understanding the function of β2-adrenergic receptor gene (ADRβ2) on disease susceptibility, pulmonary function, and therapeutic responses in different ethnic groups with asthma. Objectives: To identify ADRβ2 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 ADRβ2 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 (Gly 16Arg) 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 ADRβ2 may influence lung function, andmay be important in delineating variation in β-agonist responses, especially in African Americans.

Original languageEnglish (US)
Pages (from-to)1101-1109
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume174
Issue number10
DOIs
StatePublished - Nov 15 2006
Externally publishedYes

Keywords

  • Asthma
  • Dna polymorphisms
  • Pharmacogenomics
  • β-agonist therapy
  • β2-adrenergic receptor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Fingerprint

Dive into the research topics of 'Sequence, haplotype, and association analysis of ADRβ2 in a multiethnic asthma case-control study'. Together they form a unique fingerprint.

Cite this