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- Castro-Giner, F., et al.
(author)
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Joint effect of obesity and TNFA variability on asthma : two international cohort studies
- 2009
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 33:5, s. 1003-1009
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Journal article (peer-reviewed)abstract
- Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7-3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1-1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5-14.4; OR for G/G genotype 1.7, 95% CI 0.8-3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.
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- Castro-Giner, F., et al.
(author)
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Positionally cloned genes and age-specific effects in asthma and atopy : an international population-based cohort study (ECRHS)
- 2010
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In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 65:2, s. 124-131
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Journal article (peer-reviewed)abstract
- Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990-2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p < 0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.
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- Rebordosa, C, et al.
(author)
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ADRB2 Gly16Arg polymorphism, asthma control and lung function decline
- 2011
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 38:5, s. 1029-1035
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Journal article (peer-reviewed)abstract
- Arg/Arg homozygotes for the Gly16Arg polymorphism in the β(2)-adrenoreceptor gene (ADRB2) have a reduced response to short-acting β(2)-agonists but no effect has been associated with long-acting β(2)-agonists (LABAs). We selected 604 subjects with current asthma from the European Community Respiratory Health Study to evaluate whether asthma control and lung function decline were associated with Gly16Arg polymorphism, and to test whether LABA or inhaled corticosteroid (ICS) use modified these effects. There was an increased risk of noncontrolled asthma (OR 1.33, 95% CI 1.01-1.75; p=0.046) for each Arg allele. Among nonusers of ICS, the odds ratio of noncontrolled asthma among Arg/Arg versus Gly/Gly subjects was 2.73 (95% CI 1.28-5.82; p=0.009). No increased risk of noncontrolled asthma associated with the Arg allele was observed among ICS and/or LABA users. For each Arg allele, a mean±se decrease in decline in forced expiratory volume in 1 s of 7.7±2.5 mL·yr(-1) was found (p-value for trend 0.003), irrespective of ICS or LABA use. Arg/Arg subjects had an increased risk of bronchial hyperresponsiveness (BHR) versus Gly/Gly subjects, with an odds ratio of 2.51 (95% CI 1.12-5.63; p=0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and BHR. Absence of genotypic effects on asthma control among ICS users may be due to reversed β(2)-adrenoreceptor desensitisation.
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