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Published ahead of print on March 11, 2005, doi:10.1164/rccm.200410-1312OC
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American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 1358-1362, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200410-1312OC

Original Article

G-Protein–coupled Receptor Polymorphisms Are Associated with Asthma in a Large German Population

Michael S. D. Kormann, David Carr, Norman Klopp, Thomas Illig, Wolfgang Leupold, Christian Fritzsch, Stephan K. Weiland, Erika von Mutius and Michael Kabesch

University Children's Hospital, Ludwig Maximilian's University Munich, Munich; Institute of Epidemiology, GSF–Research Centre for Environment and Health, Neuherberg; University Children's Hospital Dresden, Dresden; University Children's Hospital Leipzig, Leipzig; and Institute of Epidemiology, University of Ulm, Ulm, Germany

Correspondence and requests for reprints should be addressed to Michael Kabesch, M.D., University Children's Hospital, Ludwig Maximilian's University Munich, Lindwurmstrasse 4, D-80337 München, Germany. E-mail: michael.kabesch{at}med.uni-muenchen.de

Rationale: Recently, a new asthma susceptibility gene, GPRA (G-protein–related receptor for asthma), has been identified by positional cloning. Initial association studies in a Finnish and Canadian population suggested an association with asthma and elevated serum IgE levels. Objective: In a large, nested case-control study, associations between GPRA polymorphisms, asthma, and serum IgE levels were analyzed. Methods: Using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology, 1,872 German children aged 9 to 11 years (including 624 children with asthma and/or bronchial hyperresponsiveness) were genotyped for seven polymorphisms in the GPRA gene. Measurements: Hardy-Weinberg equilibrium was assessed, and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. Main Results: SNP 546333 increased the risk for asthma (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.04–1.88; p = 0.025) and concomitant asthma and bronchial hyperresponsiveness (BHR; OR, 2.38; 95% CI, 1.22–4.66; p = 0.009). Also, SNP 585883 was associated with asthma (OR, 1.34; 95% CI, 1.04–1.72; p = 0.022) and asthma in combination with BHR (OR, 2.71; 95% CI, 1.45–5.09; p = 0.001). Furthermore, SNP 585883 was associated with elevated serum IgE levels (OR, 1.63; 95% CI, 1.10–2.42; p = 0.015). Haplotype combinations of risk alleles increased the OR for asthma to 1.83 (95% CI, 1.08–3.08; p = 0.024) and for asthma and concomitant BHR to OR 3.51 (95% CI, 1.08–11.37; p = 0.036). Conclusions: These results indicate that GPRA polymorphisms increase the susceptibility for asthma and BHR, and to a lesser degree for the elevation of serum IgE, in a German population, confirming initial observations in other white populations.

Key Words: asthma • children • GPRA • IgE • polymorphism




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