title: Haplotype analysis of the endothelial nitric oxide synthase gene in asthma.
abstract: Nitric oxide (NO) is an important mediator of physiologic processes in the airways. Evidence exists that genetic factors affect NO formation and contribute to the pathophysiology of asthma. The aims of this study were to determine the endothelial NO synthase (eNOS) haplotypes in Czech asthmatics and control subjects and examine their relation to asthma. We analyzed a total of six polymorphisms. Two SNPs in the promoter (C-786T and C-691T), two variants in the introns (27-bp repeat in intron 4 and G11T in intron 23), and two others in the exons (C774T in exon 6 and G894T in exon 7) were genotyped in 610 subjects (asthma, n = 294; healthy controls, n = 316), and a case-control association study was conducted. No significant differences in allele or genotype frequencies for individual polymorphisms were observed between patients with asthma and controls after correction for multiple comparisons. Nevertheless, a G to T exchange in intron 23 was related with specific sensitization for feather (p = 0.008, p(corr) < 0.05). However, the common haplotype -786T/-691C/27-bp 5 repeat variant/774C/894G/11T was associated with lower risk of asthma (p = 0.001, p(corr) < 0.05, odds ratio = 0.58, 95% confidence interval = 0.46-0.73). These findings suggest that endothelial NOS variants may be one of the factors participating in protection or susceptibility to asthma in our population.
authors.affiliation: Department of Pathophysiology, Medical Faculty, Masaryk University Brno, Brno, Czech Republic. holla@med.muni.cz
authors.forename: Lydie Izakovicova
authors.initials: LI
authors.lastname: Holla
authors.forename: Michal
authors.initials: M
authors.lastname: Jurajda
authors.forename: Petr
authors.initials: P
authors.lastname: Pohunek
authors.forename: Vladimír
authors.initials: V
authors.lastname: Znojil
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D018153:Czech Republic / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III