NEW YORK (Reuters Health) - Single nucleotide polymorphisms (SNPs) in the A disintegrin and metalloproteinase (ADAM) 33 gene have only modest effects on asthma susceptibility, according to a report in the June Journal of Allergy and Clinical Immunology.
“Several groups have noted relationships between ADAM33 SNPs and asthma, while others and we have failed to do so,” Dr. Benjamin A. Raby from the Brigham and Women’s Hospital, Boston, Massachusetts told Reuters Health. “While this means that ADAM33 alone is not the only determinant of asthma, it is likely that it is important in some people.”
Dr. Raby and colleagues genotyped 20 ADAM33 SNPs in 587 North American families of 640 childhood asthmatic patients.
Three SNP assays did not generate reliable genotype data, leaving 17 SNPs for further analysis. The authors were unable to detect significant evidence of association to asthma with any of the SNPs tested in white or in African American patients.
Among Hispanic subjects, 2 loci in strong linkage disequilibrium showed marginal evidence of association with asthma, the report indicates, but the results proved insignificant when corrected for multiple comparisons.
SNP T+2 showed a marginal association with blood eosinophil levels among white subjects, the researchers note, though the locus accounted for only 2.3% of the total heritability of blood eosinophilia. Similarly, SNPs T1 and T+1 were marginally associated with serum IgE and eosinophil levels among Hispanic subjects.
There was no evidence of an association between airway responsiveness or FEV1 with any SNP in any ethnic group, the investigators report, and haplotype analysis showed no significant association of ADAM33 haplotypes with asthma.
“Although we were not able to replicate the findings of association with ADAM33 and asthma in our cohort,” Dr. Raby said, “this does not mean that the ADAM33 molecule is not important in the pathogenesis of asthma. ADAM33 SNPs have been associated with asthma in several populations, suggesting that the gene may be important in certain populations or may confer susceptibility when interacting with important environmental factors. As we learn more about ADAM33 and how it functions in cells, we will be able to answer some of these questions.”
“Several other genes have recently been identified as asthma-susceptibility genes, including three by methods very similar to those used to identify ADAM33,” Dr. Raby added. “The hope is that as we identify most of the important asthma genes, we will be able to use markers from all of these genes together to identify individuals at the greatest risk of developing asthma, rather than using information from one gene alone.”
Source: J Allergy Clin Immunol 2004;113:1071-1078. [ 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.
