Joint effect of obesity and<i>TNFA</i>variability on asthma: two international cohort studies

Castro-Giner, Francesc; Kogevinas, Manolis; Imboden, Medea; Cid, Rafael de; Jarvis, Déborah; Mächler, M.; Berger, Wolfgang; Burney, Peter; Franklin, Karl A.; González, Juan R.; Heinrich, Joachim; Janson, Christer; Omenaas, Ernst; Pin, Isabelle; Rochat, Thierry; Sunyer, Jordi; Wjst, Matthias; Antó, JM; Estivill, Xavier; Probst‐Hensch, Nicole

doi:10.1183/09031936.00140608

Cited by 44 publications

(48 citation statements)

References 36 publications

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“…For instance, leptin stimulates and adiponectin reduces NF-κB signaling in endothelial cells (33,34), while the cytokine TNFα has been shown to interact with NF-κB signaling in ASM cells (35). We previously reported a complex joint effect of obesity with a TNFA polymorphism on asthma in two large cohort studies including SAPALDIA (7). NF-κB also exhibits a central role in the proliferating airway epithelium of asthmatics (36).…”

Section: Ccnd1 Modifies the Asthma-obesity Association 151mentioning

confidence: 99%

“…BMI, body mass index; OR, odds ratio; CI, confidence interval. molecules leptin and tumor necrosis factor alpha (TNFα) as well as the ubiquitously expressed protein kinase C alpha, a factor associated with adipocyte differentiation and insulin signaling (7,22,23). Cell cycle control genes have so far not been investigated in this respect, but their importance in inflammatory processes confer them etiologic plausibility to potentially modify the obesity-asthma relationship.…”

Section: Asthma In Obese Peoplementioning

confidence: 99%

“…Currently, there are very few studies available in adults which examine gene-obesity interactions with respect to asthma (7). Candidate genes not yet looked at include those essential to cell cycle control, as airway inflammation and remodeling in asthmatics are associated with altered apoptosis and proliferation of different bronchial cells types such as airway smooth muscle (ASM) and epithelial cells, fibroblasts, as well as cells of the immune system (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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The Association of a Variant in the Cell Cycle Control GeneCCND1and Obesity on the Development of Asthma in the Swiss SAPALDIA Study

Thun¹,

Imboden²,

Berger³

et al. 2013

Journal of Asthma

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OBJECTIVE: The molecular mechanisms underlying the association between obesity (BMI 30 kg/m(2)) and asthma are poorly understood. Since shifts in the fate of bronchial cells due to lowgrade systemic inflammation may provide a possible explanation, we investigated whether two of the best documented functional variants in cell cycle control genes modify the obesity-asthma association. METHODS: We genotyped 5930 SAPALDIA cohort participants for the single-nucleotide polymorphisms (SNPs) rs9344 in the cyclin D1 gene (CCND1) and rs1042522 in the gene encoding tumor protein 53 (TP53). We assessed the independent association of these SNPs and obesity with asthma prevalence and incidence. RESULTS: The CCND1 SNP modified the association between obesity and asthma prevalence (p(interaction )= 0.03). The odds ratios (ORs) and 95% confidence intervals (CIs) for reporting a physician diagnosis of asthma at baseline, comparing obese with non-obese participants, were 1.09 (0.51-2.33), 1.64 (0.94-2.88), and 3.51 (1.63-7.53) for GG, GA, and AA genotypes, respectively. We found comparable genotype differences for incident asthma within the 11 years of follow-up. As for the TP53 SNP, the interactions with obesity status with respect to asthma were not statistically significant. CONCLUSIONS: Our results suggest that obesity may contribute to asthma and associated tissue remodeling by modifying the processes related to the CCND1 gene activity. Objective. The molecular mechanisms underlying the association between obesity (BMI 30 kg/m 2 ) and asthma are poorly understood. Since shifts in the fate of bronchial cells due to low-grade systemic inflammation may provide a possible explanation, we investigated whether two of the best documented functional variants in cell cycle control genes modify the obesity-asthma association. Methods. We genotyped 5930 SAPALDIA cohort participants for the single-nucleotide polymorphisms (SNPs) rs9344 in the cyclin D1 gene (CCND1) and rs1042522 in the gene encoding tumor protein 53 (TP53). We assessed the independent association of these SNPs and obesity with asthma prevalence and incidence. Results. The CCND1 SNP modified the association between obesity and asthma prevalence (p interaction ¼ 0.03). The odds ratios (ORs) and 95% confidence intervals (CIs) for reporting a physician diagnosis of asthma at baseline, comparing obese with non-obese participants, were 1.09 (0.51-2.33), 1.64 (0.94-2.88), and 3.51 (1.63-7.53) for GG, GA, and AA genotypes, respectively. We found comparable genotype differences for incident asthma within the 11 years of follow-up. As for the TP53 SNP, the interactions with obesity status with respect to asthma were not statistically significant. Conclusions. Our results suggest that obesity may contribute to asthma and associated tissue remodeling by modifying the processes related to the CCND1 gene activity.of Asthma, 2013; 50(2): 147-154 Copyright © 2013 Informa Healthcare USA, Inc. ISSN: 0277-0903 print/1532-4303

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Section: Ccnd1 Modifies the Asthma-obesity Association 151mentioning

confidence: 99%

Section: Asthma In Obese Peoplementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Association of a Variant in the Cell Cycle Control GeneCCND1and Obesity on the Development of Asthma in the Swiss SAPALDIA Study

Thun¹,

Imboden²,

Berger³

et al. 2013

Journal of Asthma

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“…Genotyping and quality control for the rs1042713 polymorphism in the ADRB2 gene were performed as a part of more extensive genotyping at the Centre for Genomic Regulation of the Spanish National Genotyping Centre (Barcelona, Spain), as described previously [15].…”

Section: Genotypingmentioning

confidence: 99%

ADRB2Gly16Arg polymorphism, asthma control and lung function decline

Rebordosa¹,

Kogevinas

Guerra

et al. 2011

Eur Respir J

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Arg/Arg homozygotes for the Gly16Arg polymorphism in the b 2 -adrenoreceptor gene (ADRB2) have a reduced response to short-acting b 2 -agonists but no effect has been associated with long-acting b 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; p50.046) 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; p50.009). 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; p50.025) 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 b 2 -adrenoreceptor desensitisation.

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“…TNF-alpha haplotypes have been associated with asthma and airway hyperresponsiveness 10 and with obesity 11 . TNF-alpha and IL-6 are produced by adipocytes and correlate with total body fat 12 and TNF-alpha increases production of IL-6 in both obesity and asthma 13 .…”

Section: Introductionmentioning

confidence: 99%

Impact of weight loss on markers of systemic inflammation in obese Saudi children with asthma

El-Kader

Al-Jiffri²,

Ashmawy³

2013

Afr H. Sci.

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Background: Weight loss studies were conducted in children without asthma have demonstrated a reduction in systemic inflammation. However, the impact of weight loss in the obese paediatric population with asthma has not been investigated. Objective: To measure the effects of weight loss on markers of systemic inflammation in obese children with bronchial asthma. Methods: Eighty obese children with bronchial asthma (42 boys, and 38 girls) with mean age 13.86± 3.21 years were divided into two equal groups. The training group received diet regimen, exercise training in addition to the medical treatment for two months, where the control group received the medical treatment only.Results: There was a 17.5% , 15.5% , 22.4% , 14.1% and 15.9% reduction in mean values of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), Leptin and body mass index (BMI) respectively and 38.7 % increase in mean values of adiponectin in the training group. While, there was a 0.7% , 9.0% , 2.8% , 1.6% and 1.2% increase in mean values of TNF-alpha, IL-6, IL-8, Leptin and BMI respectively and 3.9% decrease in mean values of adiponectin in the control group. The mean values of TNF-alpha, IL-6, IL-8, Leptin and BMI was decreased and adiponectin was increased significantly in the training group, however the results of the control group were not significant. Also, there were significant differences between both groups at the end of the study. Conclusion: Weight loss improves markers of systemic inflammation in obese Saudi children with bronchial asthma.

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Joint effect of obesity andTNFAvariability on asthma: two international cohort studies

Cited by 44 publications

References 36 publications

The Association of a Variant in the Cell Cycle Control GeneCCND1and Obesity on the Development of Asthma in the Swiss SAPALDIA Study

The Association of a Variant in the Cell Cycle Control GeneCCND1and Obesity on the Development of Asthma in the Swiss SAPALDIA Study

ADRB2Gly16Arg polymorphism, asthma control and lung function decline

Impact of weight loss on markers of systemic inflammation in obese Saudi children with asthma

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