NEW YORK (Reuters Health) - Polymorphisms in the ADAM33 gene may account for a substantial excess number of asthma diagnoses, according to a report in the April issue of Thorax.
“Asthma has a clear genetic component,” Dr. Ian P. Hall from Queen’s Medical Centre, Nottingham, UK told Reuters Health. “A number of genes each of moderate effect will contribute to the risk of an individual developing asthma: ADAM33 is one of these genes...but to build useful predictive models we will need to define all of the main contributors.”
Dr. Hall and colleagues investigated the contribution of ADAM33 polymorphisms to asthma risk in more than 400 families and conducted a meta-analysis of published data to clarify the risk associated with such polymorphisms.
None of the polymorphisms appeared to be associated with asthma in their own patient population, the authors report, but four single-nucleotide polymorphisms (SNPs) were associated with an increased risk of asthma when all available data were combined.
In another analysis, again using all available data, four SNPs were transmitted more commonly than predicted to subjects with asthma.
Only two SNPs (F+1 and ST+7) proved significant in both analyses, the researchers note, and they were in tight linkage disequilibrium in the Icelandic control population.
Based on the prevalence of these alleles, the investigators report, the ST+7 SNP could contribute around 50,000 excess asthma cases in the UK population.
“Even larger populations will be needed to study epigenetic and gene-environment interactions effectively in order to derive an accurate predictive model for the risk of an individual developing asthma,” the researchers conclude.
ADAM33 polymorphisms will probably “be a minor to moderate contributor to the population risk of asthma based on our studies,” Dr. Hall said.
“We are planning to undertake what I believe will be the largest association study of asthma and related phenotypes using the UK 1958 birth cohort, genotyping a number of potential asthma candidate genes in 8000 individuals,” Dr. Hall added. “We also work on pharmacogenetics and have a number of ongoing studies on response to treatment in asthmatics.”
“There is still much to find out about this fascinating and complex molecule in relation to the development and progression of asthma,” write Dr. S. T. Holgate and Dr. J. W. Holloway from Southampton General Hospital, Southampton, UK in a related editorial. “We are now entering the new research era of translational science and the rebirth of experimental medicine as a research focus.”
Source: Thorax 2005;60:274-276,263-264. [ Google search on this article ]
MeSH Headings:Polymorphism, Single NucleotideCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
