by Gene Emery
Last Updated: 2009-12-24 16:57:00 -0400 (Reuters Health)
BOSTON (Reuters) – A defective gene appears to contribute to most cases of childhood asthma, a finding that could lead to a better understanding of allergies, U.S. researchers reported on Wednesday.
The discovery "is very likely to extend beyond asthma and really be a key player in all allergies. Because about 30% of the population has allergies, there’s a lot of potential here," Dr. Hakon Hakonarson of The Children’s Hospital of Philadelphia, who led the study, said in a telephone interview.
"There are a number of genes that have been reported to play a role in asthma. They are either false alarms or their role in asthma is a lot weaker or smaller than we expected them to be, otherwise we would have seen them with this approach," he said.
Dr. Hakonarson said allergies are involved in about 85% of childhood asthma cases, and 80% to 90% of those children have the defective gene.
According to their article published online December 23 in The New England Journal of Medicine, Dr. Hakonarson and his colleagues conducted a genomewide association study in 793 asthmatic children of European ancestry and 1988 matched controls. The patients all required daily inhaled glucocorticoid therapy. After that analysis, the researchers did another genomewide association study in a similar cohort of 917 asthmatic children and 1546 matched controls, to replicate their findings.
"Finally," they said, they looked for an association between 20 single-nucleotide polymorphisms (SNPs) at chromosome 1q31 and asthma in 1667 asthmatic children of African ancestry and 2045 matched controls.
Ultimately, the researchers continue, they saw an association between moderate to severe asthma and SNPs at a previously reported locus (on 17q21), but they also found associations with eight previously unreported SNPs at a locus on 1q31.
"The SNP most strongly associated with asthma was rs2786098," the authors report. They add, "The 1q31 locus contains DENND1B, a gene that is expressed by natural killer cells and dendritic cells and that encodes a protein that interacts with the tumor necrosis factor receptor."
"Other asthma-related genes remain to be discovered, but finding a way to target this common gene variant could benefit large numbers of children," Dr. Hakonarson said in a statement.
"Two genes lie in the implicated chromosomal region at 1q31; DENND1B is the stronger of the two candidate genes with respect to conferring…susceptibility to asthma, since not only does it encode a protein with a putative role in the adaptive immune system but part of it also lies within the minimum shared interval that is most significantly associated with asthma in persons of both European and African ancestry," the article concludes.
N Engl J Med 2009.