Analysis of the inducible nitric oxide synthase gene polymorphisms in Czech patients with atopic diseases

Abstract

Nitric oxide (NO) is an important mediator of physiologic processes in the airways; it plays a significant role in the regulation of the T helper type 1/type 2 balance and contributes to the development of atopic diseases. We analysed several polymorphisms mainly in the promoter region of the inducible NO synthase (NOS2, iNOS) gene and investigated their associations with asthma and/or atopic phenotypes. We performed a case-control study in 994 subjects (661 patients with atopic disorders, with subgroups of 304 patients with allergic asthma, and 333 healthy individuals), matched for sex, living in the same geographical area. Screening for polymorphisms was performed by combination of PCR and direct sequencing analysis. We analysed 14 nucleotide sequence variants, seven most common of which were typed in quite large groups of our asthmatic, atopic and control populations. None of these seven frequent polymorphisms was associated with the phenotype bronchial asthma or other atopic diseases. Nevertheless, three from six common promoter polymorphisms showed a significant relation to feather's positivity (P value from 0.01 to 0.03) and the NOS2 608Leu variant was significantly associated with asthma severity [p(corr) = 0.0005; odds ratio (OR) = 5.00, 95% confidence interval (CI): 1.88-13.33]. In haplotype analysis, the most common -2447C/-1659C/-1026G/-0.7del/-277A/Ser608 haplotype was associated with a lower risk of asthma when compared with the common haplotypes with frequency more than 5% (P = 0.01, p(corr) < 0.05; OR = 0.65, 95% CI: 0.56-0.77). Our findings suggest that inducible NOS can play a role in atopic disorders, and several polymorphisms in its gene may be important for asthma protection or susceptibility.