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Am. J. Respir. Crit. Care Med., Volume 162, Number 2, August 2000, 599-602

beta 2-Adrenergic Receptor Arg16/Arg16 Genotype Is Associated with Reduced Lung Function, but Not with Asthma, in the Hutterites

ELEANOR SUMMERHILL, STEPHANIE A. LEAVITT, HEIDI GIDLEY, RODNEY PARRY, JULIAN SOLWAY, and CAROLE OBER

Departments of Human Genetics and Medicine, University of Chicago, Chicago, Illinois; and Department of Medicine, University of South Dakota Medical School, Sioux Falls, South Dakota

In a genome-wide screen for asthma loci in the Hutterites, a marker locus on chromosome 5q23-31 showed evidence of linkage to asthma (C. Ober and colleagues, Hum. Molec. Genet. 1998;7:1393). To determine whether the beta 2-adrenergic receptor (beta 2AR) gene is the 5q-linked asthma locus in the Hutterites, we genotyped this sample for polymorphisms in the beta 2AR gene. Neither the Arg16Gly nor Gln27Glu polymorphisms showed evidence of linkage to qualitative measures of asthma and bronchial hyperresponsiveness (BHR) (p > 0.10) or to quantitative measures of serum IgE and airway reactivity (p > 0.10). In contrast, FEV1 percentage of predicted and FVC percentage of predicted were significantly lower among individuals homozygous for the Arg16 allele (FEV1 %: 98.3 ± 13.2% versus 103.8 ± 14.9%, p = 0.003; FVC %: 104.2 ± 12.3% versus 108.3 ± 13.2%, p = 0.02 by t test). These findings held true for adolescents and adults, but not for children =< 12 yr of age. This study demonstrates that the observed linkage to asthma in the 5q23-31 region is unrelated to variation in the beta 2AR gene. However, it is the first study to suggest that the beta 2AR Arg16Gly polymorphism influences either lung growth or the rate of decline of lung function with age.




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