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

• Published in: American journal of respiratory and critical care medicine 2005-06, Vol.171 (12), p.1358-1362
• Main Authors: Kormann, Michael S. D, Carr, David, Klopp, Norman, Illig, Thomas, Leupold, Wolfgang, Fritzsch, Christian, Weiland, Stephan K, von Mutius, Erika, Kabesch, Michael
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Asthma - epidemiology; Asthma - genetics; Asthma - immunology; Base Sequence; Biological and medical sciences; Blood and lymphatic vessels; Blood Chemical Analysis; Bronchial Provocation Tests; Cardiology. Vascular system; Child; Cohort Studies; Coronary heart disease; Cross-Sectional Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Germany - epidemiology; Heart; Humans; Intensive care medicine; Male; Medical sciences; Molecular Sequence Data; Polymerase Chain Reaction; Polymorphism, Genetic; Probability; Receptors, G-Protein-Coupled - genetics; Sensitivity and Specificity; Severity of Illness Index; Spirometry; Students
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200410-1312OC

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. In a large, nested case-control study, associations between GPRA polymorphisms, asthma, and serum IgE levels were analyzed. 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. Hardy-Weinberg equilibrium was assessed, and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. 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). 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.