Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children.
BACKGROUND
Nitric oxide (NO) is a key factor for balancing T-helper type 1/T-helper type 2 immunity. Single nucleotide polymorphisms (SNPs) in nitric oxide synthase (NOS) genes have been associated with atopy and exhaled NO concentrations in Caucasians. We investigated the association between asthma traits and genetic polymorphisms in neuronal NO synthase (NOS1) and endothelial NO synthase (NOS3) in Chinese children.


METHODS
Asthmatic children between 5 and 18 years of age and non-allergic controls were recruited. Plasma total IgE was measured by microparticle immunoassay, whereas allergen-specific IgEs were measured by fluorescent enzyme immunoassay. Fractional exhaled NO concentration (FeNO) was measured by a chemiluminescence analyser. NOS1 C5266T and NOS3 G894T were genotyped by restriction fragment length polymorphism, and (AAT)n polymorphism in intron 20 of NOS1 was determined by GeneScan analysis.


RESULTS
The mean (SD) ages of 295 asthmatics and 174 controls were 11.1 (3.8) years and 11.6 (4.0) years, respectively (P=0.162). NOS1 C5266T and NOS3 G894T were not associated with asthma, atopy or FeNO. However, significantly more subjects with T/T in NOS1 C5266T had increased plasma total IgE as compared with those with C/T or C/C (P=0.017). This SNP was also associated with sensitization to Dermatophagoides pteronyssinus (P=0.049). Among asthmatic patients, log-transformed plasma total IgE levels were significantly higher among those homozygous for 5266T of NOS1 [mean (SD): 2.84 (0.44) for T/T, 2.68 (0.42) for C/T, 2.59 (0.69) for C/C; P=0.021]. This study found a significant inter-ethnic difference in the allele frequencies of AAT repeats, and this polymorphism was associated with high plasma total IgE levels (P=0.044) but not FeNO (P=0.158). NOS3 G894T was not associated with any asthma or atopy phenotype.


CONCLUSIONS
NOS1 C5266T and AAT repeats affect plasma IgE concentrations in Chinese children. On the other hand, neither NOS1 nor NOS3 SNP was associated with FeNO or the risk of having asthma.
Leung
T F
TF
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China. tfleung@cuhk.edu.hk
Liu
E K H
EK
Tang
N L S
NL
Ko
F W S
FW
Li
C Y
CY
Lam
C W K
CW
Wong
G W K
GW
D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D001944:Breath Tests; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable
D009569:Nitric Oxide; D007073:Immunoglobulin E; C496320:NOS1 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III