Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients with atopic asthma.
BACKGROUND
Asthma is a common multifactorial disease, the aetiology of which is attributable to both environmental and genetic factors. The endothelial nitric oxide synthase (NOS3) gene has been implicated in asthma pathogenesis.


OBJECTIVE
This study investigated associations of 27 base-pair tandem repeat polymorphism in intron 4 and the Glu298Asp (G894T) variant of the NOS3 gene with atopic asthma in a Czech population.


METHODS
Polymerase chain reaction was used to determine the NOS3 genotypes in subjects with atopic asthma (n = 163) and random controls (n = 209).


RESULTS
The NOS3 allele or genotype distributions did not differ significantly between the control and asthma groups. However, the common genotype (bb) of the NOS3 polymorphism in intron 4 was found to be significantly associated with total IgE levels (P = 0.006), specific IgE levels for feathers (P = 0.0002) and a positive skin prick test for hay (P = 0.004). In one atopic patient, we identified an additional 27-bp repeat in the NOS3 gene (NOS3c), which occurred in heterozygous combination with the NOS3b allele (NOS3b/c genotype). In addition, we describe a new polymorphism (A5495G) in the NOS3 gene, which was in almost complete linkage disequilibrium with the NOS3 repeat polymorphism in intron 4. The Glu298Asp variant was not associated with asthma and/or related atopic phenotypes in our study.


CONCLUSIONS
Neither the NOS3 'b' allele nor the NOS3 'b/b' genotype showed any general association with atopic asthma, but they were associated with atopy-related phenotypes. We conclude that the NOS3 gene polymorphisms may act as disease modifiers in atopic asthma phenotype in our population.
Institute of Pathological Physiology, Masaryk University Brn. Czch Republic. holla@med.muni.cz
L I
LI
Hollá
D
D
Bucková
V
V
Kuhrová
A
A
Stejskalová
H
H
Francová
V
V
Znojil
J
J
Vácha
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018153:Czech Republic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012882:Skin Tests; D018709:Statistics, Nonparametric
D007073:Immunoglobulin E; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III