Nitric Oxide Synthase 2 Promoter Polymorphism Is a Risk Factor for Allergic Asthma in Children

Background and Objectives: In paediatric population, atopic asthma is associated with increased eosinophil counts in patients, that correlate with the airway inflammation measured by the concentration of nitric oxide in exhaled air (FeNO). As the FeNO level is a biomarker of atopic asthma, we assumed that polymorphisms in nitric synthases genes may represent a risk factor for asthma development. The purpose of this study was to analyse the association of NOS genetic variants with childhood asthma in the Polish population. Materials and methods: In study we included 443 children—220 patients diagnosed with atopic asthma and 223 healthy control subjects. We have genotyped 4 single nucleotide polymorphisms (SNP) from 3 genes involved in the nitric oxide synthesis (NOS1, NOS2 and NOS3). All analyses were performed using polymerase chain reaction with restriction fragments length polymorphism (PCR-RFLP). Results: We observed significant differences between cases and controls in SNP rs10459953 in NOS2 gene, considering both genotypes (p = 0.001) and alleles (p = 0.0006). The other analyzed polymorphisms did not show association with disease. Conclusions: According to our results, 5′UTR variant within NOS2 isoform may have an impact of asthma susceptibility in the population of Polish children. Further functional studies are required to understand the role of iNOS polymorphism in NOS2 translation and to consider it as a novel risk factor in childhood asthma. The next step would be to apply this knowledge to improve diagnosis and develop novel personalized asthma therapies.

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No Association ofIFNG+874T/ASNP andNOS2A-954G/CSNP Variants with Nitric Oxide Radical Serum Levels or Susceptibility to Tuberculosis in a Brazilian Population Subset

BioMed Research International ◽

10.1155/2013/901740 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Ana Cristina C. S. Leandro ◽

Márcia Andrade Rocha ◽

Andreia Lamoglia-Souza ◽

John L. VandeBerg ◽

Valeria Cavalcanti Rolla ◽

...

Keyword(s):

Nitric Oxide ◽

Serum Levels ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Nitric Oxide Radical ◽

Study Population ◽

Host Genetic ◽

Nitric Oxide Synthase 2 ◽

Oxide Synthase ◽

Control Study

Tuberculosis (TB) is one of the most common infectious diseases in the world.Mycobacterium tuberculosisinfection leads to pulmonary active disease in approximately 5–10% of exposed individuals. Both bacteria- and host-related characteristics influence latent infection and disease. Host genetic predisposition to develop TB may involve multiple genes and their polymorphisms. It was reported previously that interferon gamma (IFN-γ) and nitric oxide synthase 2 (NOS2) are expressed on alveolar macrophages from TB patients and are responsible for bacilli control; thus, we aimed this study at genotyping single nucleotide polymorphismsIFNG+874T/ASNP andNOS2A-954G/CSNP to estimate their role on TB susceptibility and determine whether these polymorphisms influence serum nitrite andNOx-production. This case-control study enrolled 172 TB patients and 179 healthy controls. Neither polymorphism was associated with susceptibility to TB.NOS2A-954G/CSNP was not associated with serum levels of nitrite andNOx-. These results indicate that variants ofIFNG+874T/ASNP andNOS2A-954G/CSNP do not influence TB susceptibility or the secretion of nitric oxide radicals in the study population.

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Association of (CCTTT)10, a nitric oxide synthase 2 promoter polymorphism, with death due to acute lung injury

Critical Care ◽

10.1186/cc6684 ◽

2008 ◽

Vol 12 (Suppl 2) ◽

pp. P463

Author(s):

D Perez ◽

C Manzon ◽

J Navellou ◽

C Patry ◽

G Capellier

Keyword(s):

Nitric Oxide ◽

Acute Lung Injury ◽

Nitric Oxide Synthase ◽

Lung Injury ◽

Promoter Polymorphism ◽

Nitric Oxide Synthase 2 ◽

Oxide Synthase

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Inducible nitric oxide synthase 2 promoter polymorphism and malaria disease severity in children in Southern Ghana

PLoS ONE ◽

10.1371/journal.pone.0202218 ◽

2018 ◽

Vol 13 (8) ◽

pp. e0202218

Author(s):

Mawuli Dzodzomenyo ◽

Anita Ghansah ◽

Nana Ensaw ◽

Benjamin Dovie ◽

Langbong Bimi ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Disease Severity ◽

Inducible Nitric Oxide Synthase ◽

Promoter Polymorphism ◽

Nitric Oxide Synthase 2 ◽

Oxide Synthase ◽

Southern Ghana ◽

Inducible Nitric Oxide

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The 20210 A Allele of the Prothrombin Gene Is a Common Risk Factor among Swedish Outpatients with Verified Deep Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657674 ◽

1997 ◽

Vol 78 (03) ◽

pp. 0990-0992 ◽

Cited By ~ 161

Author(s):

Andreas Hillarp ◽

Bengt Zӧller ◽

Peter J Svensson ◽

Bjӧrn Dahlbäck

Keyword(s):

Risk Factor ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Odds Ratio ◽

Untranslated Region ◽

Control Group ◽

Common Risk Factor ◽

Apc Resistance ◽

Healthy Control ◽

Prothrombin Gene

SummaryA dimorphism in the 3’-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis (1). We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% Cl, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% Cl, 1.1 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.

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Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea

Allergy and Asthma Proceedings ◽

10.2500/aap.2019.40.190007 ◽

2020 ◽

Vol 41 (2) ◽

pp. 134-140

Author(s):

Yuriy Bisyuk ◽

Andrew Dubovyi ◽

Ilona DuBuske ◽

Viktor Litus ◽

Lawrence M. DuBuske

Keyword(s):

Late Onset ◽

Adult Population ◽

Additive Models ◽

Atopic Asthma ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Single Nucleotide ◽

Gender And Age

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00‐2.32] and overdominant (OR 1.55 [95% CI, 1.01‐2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07‐0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.

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Faculty Opinions recommendation of A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1000925.158657 ◽

2002 ◽

Author(s):

Ferric Fang

Keyword(s):

Nitric Oxide ◽

Severe Malaria ◽

Promoter Polymorphism ◽

Nitric Oxide Production ◽

Oxide Production

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Household mold exposure interacts with inflammation-related genetic variants on childhood asthma: a case–control study

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01484-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yu Zhang ◽

Li Hua ◽

Quan-Hua Liu ◽

Shu-Yuan Chu ◽

Yue-Xin Gan ◽

...

Keyword(s):

Childhood Asthma ◽

Case Control Study ◽

Additive Model ◽

Case Control ◽

Nucleotide Polymorphisms ◽

Additive Interaction ◽

Asthmatic Children ◽

Gene Environment ◽

Mold Exposure ◽

Control Study

Abstract Background A number of studies have examined the association between mold exposure and childhood asthma. However, the conclusions were inconsistent, which might be partly attributable to the lack of consideration of gene function, especially the key genes affecting the pathogenesis of childhood asthma. Research on the interactions between genes and mold exposure on childhood asthma is still very limited. We therefore examined whether there is an interaction between inflammation-related genes and mold exposure on childhood asthma. Methods A case–control study with 645 asthmatic children and 910 non-asthmatic children aged 3–12 years old was conducted. Eight single nucleotide polymorphisms (SNPs) in inflammation-related genes were genotyped using MassARRAY assay. Mold exposure was defined as self-reported visible mold on the walls. Associations between visible mold exposure, SNPs and childhood asthma were evaluated using logistic regression models. In addition, crossover analyses were used to estimate the gene-environment interactions on childhood asthma on an additive scale. Results After excluding children without information on visible mold exposure or SNPs, 608 asthmatic and 839 non-asthmatic children were included in the analyses. Visible mold exposure was reported in 151 asthmatic (24.8%) and 119 non-asthmatic children (14.2%) (aOR 2.19, 95% CI 1.62–2.97). The rs7216389 SNP in gasdermin B gene (GSDMB) increased the risk of childhood asthma with each C to T substitution in a dose-dependent pattern (additive model, aOR 1.32, 95% CI 1.11–1.57). Children carrying the rs7216389 T allele and exposed to visible mold dramatically increased the risk of childhood asthma (aOR 3.21; 95% CI 1.77–5.99). The attributable proportion due to the interaction (AP: 0.47, 95% CI 0.03–0.90) and the relative excess risk due to the interaction (RERI: 1.49, 95% CI 0–2.99) were statistically significant. Conclusions In the present study, there was a significant additive interaction between visible mold exposure and rs7216389 SNP on childhood asthma. Future studies need to consider the gene-environment interactions when exploring the risk factors of childhood asthma.

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Effects of AGXT2 variants on blood pressure and blood sugar among 750 older Japanese subjects recruited by the complete enumeration survey method

BMC Genomics ◽

10.1186/s12864-021-07612-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yuta Yoshino ◽

Hiroshi Kumon ◽

Takaaki Mori ◽

Taku Yoshida ◽

Ayumi Tachibana ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Blood Sugar ◽

Vascular Diseases ◽

Survey Method ◽

Nucleotide Polymorphisms ◽

Complete Enumeration ◽

Plasma Adma ◽

Oxide Synthase ◽

Japanese Subjects

Abstract Background Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) is the only enzyme that degrades the R-form of 3-aminoisobutyrate, an intermediate metabolite of thymine. AGXT2, as well as diaminoarginine dimethylaminohydrolase 1 (DDAH1; EC 3.5.3.18), works as an enzyme that degrades asymmetric dimethylarginine (ADMA), which competitively inhibits the nitric oxide synthase family. Thus, these two enzyme activities may change vascular vulnerability for a lifetime via the nitric oxide (NO) system. We investigated the association between vascular conditions and diseases such as hypertension and diabetes mellitus and polymorphisms of these two genes in 750 older Japanese subjects (mean age ± standard deviation, 77.0 ± 7.6 years) recruited using the complete enumeration survey method in the Nakayama study. Demographic and biochemical data, such as blood pressure (BP) and casual blood sugar (CBS), were obtained. Four functional single nucleotide polymorphisms (SNPs; rs37370, rs37369, rs180749, and rs16899974) of AGXT2 and one functional insertion/deletion polymorphism in the promotor region with four SNPs (rs307894, rs669173, rs997251, and rs13373844) of DDAH1 were investigated. Plasma ADMA was also analyzed in 163 subjects. Results The results of multiple regression analysis showed that a loss of the functional haplotype of AGXT2, CAAA, was significantly positively correlated with BP (systolic BP, p = 0.034; diastolic BP, p = 0.025) and CBS (p = 0.021). No correlation was observed between DDAH1 and either BP or CBS. ADMA concentrations were significantly elevated in subjects with two CAAA haplotypes compared with subjects without the CAAA haplotype (p = 0.033). Conclusions Missense variants of AGXT2, but not DDAH1, may be related to vulnerability to vascular diseases such as hypertension and DM via the NO system.

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