Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:120

Article

Wu, Hao ; Romieu, Isabelle ; Sienra-Monge, Juan-Jose ; del Rio-Navarro, Blanca Estela ; Anderson, Daniel M. ; Jenchura, Charlotte A. ; Li, Huiling ; Ramirez-Aguilar, Matiana ; Lara-Sanchez, Irma del Carmen ; London, Stephanie J.

关键词: alcohol dehydrogenase 5;    allergy;    asthma;    formaldehyde dehydrogenase;    genetic predisposition to disease;    nitric oxide;    single nucleotide polymorphism;    S-nitrosoglutathione;    S-nitrosoglutathione reductase;    S-nitrosothiol;   

DOI  :  10.1016/j.jaci.2007.04.022

来源: Elsevier

【 摘 要 】

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 rs1154404 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 rs28730619 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. Conclusion: 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. Clinical implications: The association of GSNOR polymorphisms with asthma suggests a potential therapeutic target.

【 授权许可】

Free