title: G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Hardy-Weinberg equilibrium was assessed, and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed.
  
  
  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.
authors.affiliation: University Children's Hospital, Ludwig Maximilian's University Munich, Lindwurmstrasse 4, D-80337 München, Germany.
authors.forename: Michael S D
authors.initials: MS
authors.lastname: Kormann
authors.forename: David
authors.initials: D
authors.lastname: Carr
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Leupold
authors.forename: Christian
authors.initials: C
authors.lastname: Fritzsch
authors.forename: Stephan K
authors.initials: SK
authors.lastname: Weiland
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
mesh_terms: D000704:Analysis of Variance; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001774:Blood Chemical Analysis; D001985:Bronchial Provocation Tests; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013147:Spirometry; D013334:Students
chemical_list: D043562:Receptors, G-Protein-Coupled