Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma.
BACKGROUND
S-nitrosothiols are potent endogenous bronchodilators depleted in asthmatic airway lining fluid. S-nitrosoglutathione reductase (GSNOR; also known as alcohol dehydrogenase 5 or formaldehyde dehydrogenase) catalyzes the metabolism of S-nitrosoglutathione (GSNO) and controls intracellular levels of S-nitrosothiols. GSNOR knockout mice have increased lung S-nitrosothiol levels and are therefore protected from airway hyperresponsiveness after methacholine or allergen challenge.


OBJECTIVE
We sought to investigate whether genetic variation in GSNOR is associated with childhood asthma and atopy.


METHODS
We genotyped 5 tagging and 2 additional single nucleotide polymorphisms (SNPs) in GSNOR in 532 nuclear families consisting of asthmatic children aged 4 to 17 years and both parents in Mexico City. Atopy was determined by means of skin prick testing.


RESULTS
Carrying 1 or 2 copies of the minor allele of SNP rs1,154,404 was associated with decreased risk of asthma (relative risk [RR], 0.77; 95% CI, 0.61-0.97; P = .028 for 1 copy and RR, 0.66; 95% CI, 0.44-0.99; P = .046 for 2 copies). Homozygosity for the minor allele of SNP rs28,730,619 was associated with increased risk of asthma (RR, 1.60; 95% CI, 1.13-2.26; P = .0077). Haplotype analyses supported the single SNP findings. GSNOR SNPs were not associated with the degree of atopy.


CONCLUSIONS
This is the first study of genetic polymorphisms in GSNOR and asthma. These data suggest that genetic variation in GSNOR might play a role in asthma susceptibility.


CONCLUSIONS
The association of GSNOR polymorphisms with asthma suggests a potential therapeutic target.
Wu
Hao
H
Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
Romieu
Isabelle
I
Sienra-Monge
Juan-Jose
JJ
Estela Del Rio-Navarro
Blanca
B
Anderson
Daniel M
DM
Jenchura
Charlotte A
CA
Li
Huiling
H
Ramirez-Aguilar
Matiana
M
Del Carmen Lara-Sanchez
Irma
I
London
Stephanie J
SJ
D000293:Adolescent; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide
D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent