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

Hollá, Lýdie Izakovičová; Stejskalová, Andrea; Znojil, Vladimı́r; Vašků, Anna

doi:10.1111/j.1365-2222.2006.02612.x

Cited by 25 publications

(26 citation statements)

References 39 publications

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“…However, the present sample is exclusively of Czech Caucasian origin, restricted to the limited geographical area populated by a quite homogenous population with little admixture. Third, there are certainly other genes and polymorphisms – e.g., of superoxide dismutase, nitric oxide synthase, catalase – that could modulate antioxidant properties and thus are a predisposition to asthma [30,31,32,33,34], which have not been studied in the present case.…”

Section: Discussionmentioning

confidence: 63%

Haplotype Analysis of the NADPH Oxidase p22<sup>phox</sup> Gene in Patients with Bronchial Asthma

Hollá

Kaňková²,

Znojil³

2008

Int Arch Allergy Immunol

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Background: Superoxide produced by airway epithelial and inflammatory cells may contribute to the pathogenesis of asthma. NADPH oxidase (an enzyme complex made up of 5 subunits) is a major source of superoxide in cells. We sought to elucidate the role of genetic variability in the gene encoding the p22^phox subunit of the NADPH oxidase (CYBA, 16q24.3) in asthma susceptibility by means of an association study of haplotypes based on 3 common single nucleotide polymorphisms (SNPs), –930A/G, 242C/T (H72Y) and 640A/G. Methods: SNPs were genotyped by PCR-RFLP methods in a cohort of age- and sex-matched subjects with bronchial asthma (n = 305) and healthy controls (n = 311). Haplotypes were constructed in silico using a Monte Carlo-based algorithm. Furthermore, association of SNPs with sensitization to selected allergens (total 15 tested by skin prick test positivity/negativity) was analyzed. Results: In a single locus analysis, SNPs 242C/T and 640A/G were marginally significantly associated with asthma (p = 0.036 and 0.036, respectively). SNP 640A/G showed a significant association with sensitization to 2 allergens tested (p_corr < 0.02). Haplotype analysis identified a total of 8 haplotypes with population frequencies from 0.07 to 0.22. Distribution of haplotypes significantly differed between cases and controls (omnibus p = 0.017, 10,000 permutations). In the post-hoc analysis, haplotype CYBA₃ (–930G/242T/640A) was associated with an increased risk of asthma (p_corr < 0.05; OR = 1.43, 95% CI 1.06–1.93). Conclusions: This study supports the hypothesis that genetic variability in the CYBA gene probably contributes to the susceptibility to bronchial asthma (or its related phenotypes) in our population.

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Section: Discussionmentioning

confidence: 63%

Haplotype Analysis of the NADPH Oxidase p22<sup>phox</sup> Gene in Patients with Bronchial Asthma

Hollá

Kaňková²,

Znojil³

2008

Int Arch Allergy Immunol

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“…A few reports show a direct role for iNOS in the process of eosinophil recruitment in that inhibition of iNOS, either pharmacologically or by a gene knockout, reduces airway infiltration by inflammatory cells, especially eosinophils, in models of allergen-induced lung inflammation (reviewed in [25]). Furthermore, two very recent reports showed that polymorphisms in the iNOS gene may be important for asthma protection or susceptibility [11,12]. However, the results of a recent clinical trial conducted by SINGH et al [10] questioned the role of iNOS during asthma and the viability of iNOS as a therapeutic target to treat the symptoms of the disease.…”

Section: Discussionmentioning

confidence: 92%

“…SINGH et al [10] reported that iNOS inhibition with GW274150, a selective and potent iNOS inhibitor, effectively reduces exhaled breath NO but does not affect airway inflammatory cell numbers or airway hyperreactivity after allergen challenge in subjects with asthma. Interestingly, reports by HOLLA et al [11] and BATRA et al [12] show that polymorphisms in the iNOS gene may be important for asthma protection or susceptibility. Such conflicting reports undoubtedly suggest that additional studies are necessary to fully establish the intricate role(s) of NO and its metabolites during airway inflammation.…”

Section: Synthase (Nos): Neuronal Nos (Nnos); Endothelial Nos (Enos);mentioning

confidence: 99%

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

Naura

Datta²,

Hans³

et al. 2008

European Respiratory Journal

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Inducible nitric oxide synthase (iNOS) inhibition was recently shown to exert no effect on allergen challenge in human asthma, raising serious concerns about the role of the protein in the disease. The present study investigated the role of iNOS in ovalbumin-induced eosinophilia from the perspective of its relationship with poly(ADP-ribose) polymerase-1 (PARP-1) and oxidative DNA damage.A mouse model of ovalbumin-induced eosinophilia was used to conduct the studies. iNOS-associated protein nitration and tissue damage were partially responsible for allergeninduced eosinophilia. iNOS expression was required for oxidative DNA damage and PARP-1 activation upon allergen challenge. PARP-1 was required for iNOS expression and protein nitration, and this requirement was connected to nuclear factor-kB. PARP-1 was an important substrate for iNOS-associated by-products after ovalbumin-challenge. PARP-1 nitration blocked its poly(ADPribosyl)ation activity. Interleukin-5 re-establishment in ovalbumin-exposed PARP-1 -/-mice reversed eosinophilia and partial mucus production without a reversal of iNOS expression, concomitant protein nitration or associated DNA damage.The present results demonstrate a reciprocal relationship between inducible nitric oxide synthase and poly(ADP-ribose) polymerase-1 and suggest that expression of inducible nitric oxide synthase may be dispensable for eosinophilia after interleukin-5 production. Inducible nitric oxide synthase may be required for oxidative DNA damage and full manifestation of mucus production. Such dispensability may explain, in part, the reported ineffectiveness of inducible nitric oxide synthase inhibition in preventing allergen-induced inflammation in humans.

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“…Holla et al have found in 2006 that this polymorphism can be associated with asthma susceptibility [22], whereas Johannesen et al (2001) have shown that polymorphism has been one of the most frequently encountered polymorphisms from among the 10 polymorphisms of the iNOS human gene, identified in the case of a Danish population. They have noticed an increased risk of hyperglycemia type 1 in a subgroup of positive HLA DR3/4 individuals [23].…”

Section: Discussionmentioning

confidence: 99%

The association between chronic pancreatitis and the iNOS-2087A>G polymorphism

Pădureanu

Siloşi

Forţofoiu

et al. 2017

Romanian Journal of Internal Medicine

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Introduction. Chronic pancreatitis is morphologically characterized by ductal dysplasia, breeding grounds for the proliferation of the ductal cells, the degenerative changes in pancreatic acinar cells and fibrosis, and it is defined on the basis of the clinical, morphological and functional criteria.Aim. The aim of our study is to examine the existence of a possible correlation between the iNOS-2087A>G polymorphism and chronic pancreatitis by means of the genetic analysis.Material and method. We have conducted the study at the Gastroenterology Clinic and the Research Center of Gastroenterology and Hepatology of the University of Medicine and Pharmacy, Craiova, between March 2015 – September 2016. The study had a prospective character. Both for the 58 patients diagnosed with chronic pancreatitis and for the 132 patients in the witness group, the biological material was represented by blood, (around 2.5 – 5 milliliters of venous blood) let on EDTA and kept at 4°C up to the separation of the DNA molecule. All the patients were genotyped for the iNOS – 2087A>G polymorphism, by means of the Real Time PCR technique with TaqMan probes.Results. Analysing the prevalence of the iNOS genotypes within the study group and witness group, we have noticed that, statistically speaking, there are no significant differences between the two groups.Conclusion. As a conclusion, in the study lot we can sustain that the risk of developing chronic pancreatitis is not increased by the presence of the iNOS-2087A>G polymorphism.

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

Abstract: 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.

Cited by 25 publications

References 39 publications

Haplotype Analysis of the NADPH Oxidase p22<sup>phox</sup> Gene in Patients with Bronchial Asthma

Haplotype Analysis of the NADPH Oxidase p22<sup>phox</sup> Gene in Patients with Bronchial Asthma

Reciprocal regulation of iNOS and PARP-1 during allergen-induced eosinophilia

The association between chronic pancreatitis and the iNOS-2087A>G polymorphism

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