Genetic polymorphisms in arginase I and II and childhood asthma and atopy.
BACKGROUND
A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma.


OBJECTIVE
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).


CONCLUSIONS
Variation in arginase genes may contribute to asthma and atopy in children.
Li
Huiling
H
Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Romieu
Isabelle
I
Sienra-Monge
Juan-Jose
JJ
Ramirez-Aguilar
Matiana
M
Estela Del Rio-Navarro
Blanca
B
Kistner
Emily O
EO
Gjessing
Håkon K
HK
Lara-Sanchez
Irma Del Carmen
Idel C
Chiu
Grace Y
GY
London
Stephanie J
SJ
D000293:Adolescent; D001119:Arginase / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution; C477631:ARG2 protein, human; D001119:Arginase