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


OBJECTIVE
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.
Hawkins
Gregory A
GA
Center for Human Genomics, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
Tantisira
Kelan
K
Meyers
Deborah A
DA
Ampleford
Elizabeth J
EJ
Moore
Wendy C
WC
Klanderman
Barbara
B
Liggett
Stephen B
SB
Peters
Stephen P
SP
Weiss
Scott T
ST
Bleecker
Eugene R
ER
D001741:Black or African American / Q000235:genetics; D001249:Asthma / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D005541:Forced Expiratory Volume; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
D018343:Receptors, Adrenergic, beta-2