Genetic polymorphisms in arginase I and II and childhood asthma and atopy - 15/08/11
Reprint requests: Stephanie J. London, MD, DrPH, National Institute of Environmental Health Sciences, PO Box 12233, MD A3-05, Research Triangle Park, NC 27709.Research Triangle Park, NC, Morelos and Mexico City, Mexico, and Oslo, Norway
Abstract |
Background |
A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma.
Objectives |
To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk.
Methods |
We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif).
Results |
ARG1 SNPs and haplotypes were not associated with asthma, but all 4 ARG1 SNPs were associated with the number of positive skin tests (P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR = 2.1, 95% CI = 1.2 - 3.9 with a smoking parent; RR = 1.2, 95% CI = 0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = .027).
Conclusion |
Variation in arginase genes may contribute to asthma and atopy in children.
Le texte complet de cet article est disponible en PDF.Key words : ARG1, ARG2, genetic predisposition to disease, SNP, polymorphism, single nucleotide, respiratory hypersensitivity, skin tests, asthma, tobacco smoke pollution
Abbreviations used : ARG1, ARG2, NO, NOS, RR, SNP, STAT6, TDT
Plan
| Supported by Z01 ES49019 from the Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, and grant 26206-M from the National Council of Science and Technology (CONACYT), Mexico. Dr Romieu is supported by the National Center for Environmental Health at the Centers for Disease Control. |
Vol 117 - N° 1
P. 119-126 - janvier 2006 Retour au numéro
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