Link Between Gene Variants and Asthma Confirmed by Study

The results of a large case-control study in German children confirms an association between polymorphisms in G-protein-coupled receptor genes and Asthma.

Polymorphisms of the recently identified G-protein-related receptor for asthma (GPRA) gene have been tied to high levels of serum IgE in Finnish and Canadian patients, and isoform B of the gene is overexpressed in smooth muscle cells of individuals with Asthma, Dr. Michael Kabesch of Ludwig Maximilian's University, Munich, and colleagues, report in the June 15th issue of the America Journal of Critical Care Medicine.

The researchers investigated the relationship between GPRA polymorphisms, asthma and elevated IgE in 1872 German children between 9 and 11 years old, including 624 with asthma or bronchial hyperresponsiveness.

The children were genotyped for seven known GPRA single nucleotide polymorphisms (SNP).

Two SNPs were associated with increased asthma risk, while a third was protective. Children homozygous for the protective SNP were 67% less likely to have elevated serum IgE.

While there were no statistically significant associations between bronchial hyperresponsiveness alone and any of the SNPs, when the researchers analyzed a subgroup of children with both bronchial hyperresponsiveness and asthma they found the association with the two asthma-related SNPs was even greater.

Haplotypes consisting of combined risk alleles increased asthma risk further. The single SNP with the greatest effect increased the risk of asthma and bronchial hyperresponsiveness 2.71 times, while the highest risk haplotype boosted the likelihood of asthma and bronchial hyperresponsiveness 3.51 fold.

The researchers speculate that GPRA may not only be involved in Asthma susceptibility when expressed in the lungs, but could also play a more general role in immunomodulation.

"How GPRA exerts its function in the lung and how SNPs in this gene alter such mechanisms are questions still waiting to be answered," Drs. Dirkje S. Postma and Gerard H. Koppelman of the University of Groningen in the Netherlands write in an editorial accompanying the study.

"Because many GPCRs are drug targets," they add, "the confirmation of a role for this gene in asthma clearly opens important new avenues for treatment."

Am J Resp Crit Care Med 2005;171:1358-1362,2004-2005.