| 1. |
- Dahgam, Santosh, et al.
(författare)
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Haplotypes of the inducible nitric oxide synthase gene are strongly associated with exhaled nitric oxide levels in adults: a population-based study
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:7, s. 449-454
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous genetic association studies have reported evidence for association of single-nucleotide polymorphisms (SNPs) in the NOS2 gene, encoding inducible nitric oxide synthase (iNOS), to variation in levels of fractional exhaled nitric oxide (FENO) in children and adults. In this study, we evaluated 10 SNPs in the region of chromosome 17 from 26.07Mb to 26.13Mb to further understand the contribution of NOS2 to variation in levels of FENO. Methods In a cohort of 5912 adults 25-75years of age, we investigated the relationship between NOS2 haplotypes and FENO, and effect modification by asthma. Results Seven common (frequency 5%) haplotypes (H1-H7) were inferred from all possible haplotype combinations. One haplotype (H3) was significantly associated with lower levels of FENO: -5.8% (95% CI -9.8 to -1.7; p=0.006) compared with the most common baseline haplotype H1. Two haplotypes (H5 and H6) were significantly associated with higher levels of FENO: +10.7% (95% CI 5.0 to 16.7; p=0.0002) and +14.9% (95% CI 10.6 to 19.3; p=7.8x10(-13)), respectively. The effect of haplotype H3 was mainly seen in subjects with asthma (-21.6% (95% CI -33.5 to -5.9)) and was not significant in subjects without asthma (-4.2% (95% CI -8.4 to 0.2)). The p value for interaction between H3 and asthma status was 0.004. Conclusions Our findings suggest that several common haplotypes in the NOS2 gene contribute to variation in FENO in adults. We also saw some evidence of effect modification by asthma status on haplotype H3.
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| 2. |
- Dahgam, Santosh, et al.
(författare)
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Single nucleotide polymorphisms in the NOS2 and NOS3 genes are associated with exhaled nitric oxide
- 2012
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:3, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- Background Polymorphisms in nitric oxide synthase genes (NOS1, NOS2, and NOS3) have been suggested to have a major impact on fraction of exhaled nitric oxide (FENO), a biomarker of airway inflammation. However, the genetic contribution of NOS polymorphisms to FENO is not fully understood. The aim of this study was to investigate comprehensively the association between single nucleotide polymorphisms (SNPs) in all three NOS genes and FENO in an adult population, and to assess whether such associations are modified by asthma or atopy. Method In 1737 adults from a Swedish general population sample, FENO was measured and genetic variation in the NOS genes was assessed using 49 SNPs. The genetic effect of NOS polymorphisms on FENO, asthma, and atopy was estimated using multiple regression methods. Results In a multi-SNP model based on stepwise regression analysis, two SNPs in NOS2 and one in NOS3 showed independent associations with levels of FENO. For NOS2 SNP rs9901734, subjects had 5.3% (95% CI 1.0% to 9.7%) higher levels of FENO per G allele, and for rs3729508, subjects with CC or CT genotypes had 9.4% (95% CI 3.1% to 15.2%) higher levels compared with TT. For NOS3 SNP rs7830, subjects with GT or TT had 5.6% (95% CI 0.4% to 11.1%) higher levels than GG; the genetic effect of this SNP was stronger in asthmatics (21.9%, 95% CI 4.6% to 42.0%). Conclusion These results suggest that NOS2 is the major NOS gene determining variability in exhaled nitric oxide in the healthy adult population, while NOS3 may play a more important role in asthmatic adults.
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| 3. |
- Levinsson, Anna, et al.
(författare)
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Interaction effects of long-term air pollution exposure and variants in the GSTP1, GSTT1 and GSTCD genes on risk of acute myocardial infarction and hypertension : a case-control study
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e99043-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Experimental and epidemiological studies have reported associations between air pollution exposure, in particular related to vehicle exhaust, and cardiovascular disease. A potential pathophysiological pathway is pollution-induced pulmonary oxidative stress, with secondary systemic inflammation. Genetic polymorphisms in genes implicated in oxidative stress, such as GSTP1, GSTT1 and GSTCD, may contribute to determining individual susceptibility to air pollution as a promoter of coronary vulnerability.AIMS: We aimed to investigate effects of long-term traffic-related air pollution exposure, as well as variants in GSTP1, GSTT1 and GSTCD, on risk of acute myocardial infarction (AMI) and hypertension. In addition, we studied whether air pollution effects were modified by the investigated genetic variants.METHODS: Genotype data at 7 single nucleotide polymorphisms (SNPs) in the GSTP1 gene, and one in each of the GSTT1 and GSTCD genes, as well as air pollution exposure estimates, were available for 119 AMI cases and 1310 randomly selected population controls. Population control individuals with systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or on daily antihypertensive medication were defined as hypertensive (n = 468). Individual air pollution exposure levels were modeled as annual means of NO₂ (marker of vehicle exhaust pollutants) using central monitoring data and dispersion models, linking to participants' home addresses.RESULTS: Air pollution was significantly associated with risk of AMI: OR 1.78 (95%CI 1.04-3.03) per 10 µg/m³ of long-term NO₂ exposure. Three GSTP1 SNPs were significantly associated with hypertension. The effect of air pollution on risk of AMI varied by genotype strata, although the suggested interaction was not significant. We saw no obvious interaction between genetic variants in the GST genes and air pollution exposure for hypertension.CONCLUSION: Air pollution exposure entails an increased risk of AMI, and this risk differed over genotype strata for variants in the GSTP1, GSTT1 and GSTCD genes, albeit not statistically-significantly.
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| 4. |
- Modig, Lars, et al.
(författare)
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Short-Term Exposure to Ozone and Levels of Exhaled Nitric Oxide
- 2014
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Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 25:1, s. 79-87
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adverse effects of air pollution include respiratory inflammation. A few epidemiologic studies have shown elevations in the fraction of exhaled nitric oxide, a marker of airway inflammation, after exposure to traffic-related pollutants. Methods: We examined whether short-term exposures to ozone (O-3), oxides of nitrogen (NOx), or particulate matter <10 m (PM10) were associated with proximal and distal airway inflammation. The study included 5841 randomly selected Swedish adults from 25 to 75 years of age. Fraction of exhaled nitrogen was measured at two flow rates: 50 ml/s representing the proximal airways and 270 ml/s representing the distal airways. Air pollution data were obtained from an urban monitoring site. We applied linear regression to estimate short-term associations of O-3, NOx, and PM10 with fractions of exhaled NO at 50 and 270 ml/s. Results: An interquartile range increase in 120-hour average O-3 levels was associated with a 5.1% (95% confidence interval = 1.7% to 8.5%) higher level of fraction of exhaled NO at 270 ml/s and 3.6% (-0.4% to 3.4%) higher level of the fraction of exhaled NO at 50 ml/s. For NOx, a small effect was seen for the 24-hour average on the fraction of exhaled NO at 270 ml/s, while for PM10 no clear effects were seen. There was a tendency for a weaker effect of ozone and a stronger effect of NOx in subjects with asthma. Conclusions: Exposure to O-3 was associated with a marker of distal airway inflammation, while the association was less obvious for inflammation of the proximal airways.
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