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- Levinsson, Anna, et al.
(författare)
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Nitric oxide synthase (NOS) single nucleotide polymorphisms are associated with coronary heart disease and hypertension in the INTERGENE study
- 2014
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Ingår i: Nitric oxide. - : Elsevier BV. - 1089-8603 .- 1089-8611. ; 39, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Nitric oxide synthase (NOS) exists in three distinct isoforms, each encoded by a specific gene: neuronal NOS (NOS1 gene), inducible NOS (NOS2 gene) and endothelial NOS (NOS3 gene). Single nucleotide polymorphisms (SNPs) in NOS genes have been associated with cardiovascular pathology. We aimed to comprehensively investigate which NOS gene variants are most strongly associated with coronary heart disease (CHD) and hypertension, using a set of tagging SNPs with good coverage across the 3 genes. Method and results: CHD cases (n = 560) and randomly selected population controls (n = 2791) were genotyped at 58 SNPs in the NOS genes. Control individuals with systolic blood pressure >= 140, diastolic blood pressure >= 90 or on antihypertensive medication were defined as hypertensive. A structured stepwise logistic regression approach was used to select the SNPs most strongly associated with CHD and hypertension. Method and results: NOS1 SNP rs3782218 showed the most consistent association with both phenotypes, odds ratio 0.59 (95% confidence interval 0.44-0.80) and 0.81 (0.67-0.97) per T-allele for CHD and hypertension respectively. For CHD, another NOS1 SNP (rs2682826) and a NOS3 SNP (rs1549758) also showed effect. For hypertension associations were seen for additional SNPs including NOS3 SNP rs3918226, previously associated with hypertension in genome-wide association study (GWAS) data. Conclusion: We found a previously unreported association between NOS1 SNP rs3782218 and both CHD and hypertension, and confirmed NOS1 as the most important NOS risk gene for CHD. In contrast, variants in all three NOS genes were seen to be associated with hypertension in the same source population. (C) 2014 Elsevier Inc. All rights reserved.
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- Malinovschi, Andrei, et al.
(författare)
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FeNO as a predictor of asthma control improvement after starting inhaled steroid treatment
- 2014
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Ingår i: Nitric oxide. - : Elsevier BV. - 1089-8603 .- 1089-8611. ; 40, s. 110-116
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The fraction of NO in exhaled air (FeNO) is a marker of inflammation in asthma. The aim of the present study was to assess, in a real-world setting, whether only high ( >= 50 ppb) FeNO levels predict improvement in asthma control when being treated with inhaled corticosteroids (ICS), as suggested by current guidelines on the clinical use of FeNO. Methods: FeNO and asthma control were assessed in a retrospective observational study in 153 non-smoking, steroid-nave, adult subjects with asthma with a mean age of 40 years both before and after 6 weeks (median follow-up time) of treatment with 500 mu g beclomethasone (median). Results: Having at the initial visit intermediate FeNO ( >= 25 and <50 ppb) and high FeNO ( >= 50 ppb), compared to normal FeNO (<25 ppb), were associated with a larger proportion of subjects achieving an improvement of Asthma Control Questionnaire (ACQ) score with >= 1 (78% and 67% vs 43%, p <0.05) or both >= 1 improvement and asthma control at follow-up (31% and 37% vs 4%, p < 0.05). These associations were consistent in multiple logistic regression models after adjustments for confounders. Conclusions: It is not only high but also intermediate FeNO levels that are associated with a significant improvement in asthma control after starting ICS treatment. This challenges current clinical guidelines stating that only high FeNO levels predict response to ICS treatment.
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