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Published ahead of print on March 11, 2005, doi:10.1164/rccm.200410-1312OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 12, June 2005, 1358-1362

A more recent version of this article appeared on June 15, 2005
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Submitted on October 5, 2004
Accepted on March 2, 2005

G-Protein Coupled Receptor Polymorphisms are Associated With Asthma in a Large German Population

Michael SD Kormann1, David Carr1, Norman Klopp2, Thomas Illig2, Wolfgang Leupold3, Christian Fritzsch4, Stephan K Weiland5, Erika von Mutius1, and Michael Kabesch1*

1 University Children's Hospital, Ludwig Maximilian's University, Munich, Germany, 2 GSF - Research Centre for Environment and Health, Institute of Epidemiology, Neuherberg, Germany, 3 University Children's Hospital, Dresden, Germany, 4 University Children's Hospital, Leipzig, Germany, 5 Institute of Epidemiology, University of Ulm, Ulm, Germany

* To whom correspondence should be addressed. E-mail: michael.kabesch{at}med.uni-muenchen.de.

Rationale Only 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 analysed. Methods Using MALDI-TOF technology, 1,872 German children aged 9-11 (including 624 asthmatics) were genotyped for seven polymorphisms in the GPRA gene. Measurements Hardy Weinberg equilibrium (HWE) was assessed and association studies with single SNPs and haplotypes were performed. Main Results SNP 546333 increased the risk for asthma (OR 1.40; 95% CI 1.04-1.88; p = 0.025) and concomitant asthma and 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 odds ratio 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 Caucasian populations.
Key words: asthma, IgE, GPRA, polymorphism, children




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