G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population.
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.
Kormann
Michael S D
MS
University Children's Hospital, Ludwig Maximilian's University Munich, Lindwurmstrasse 4, D-80337 München, Germany.
Carr
David
D
Klopp
Norman
N
Illig
Thomas
T
Leupold
Wolfgang
W
Fritzsch
Christian
C
Weiland
Stephan K
SK
von Mutius
Erika
E
Kabesch
Michael
M
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
D043562:Receptors, G-Protein-Coupled