Dataset Information

Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis.

ABSTRACT: Both air pollution and genetic variation have been shown to affect lung function. Their interaction has not been studied on a genome-wide scale to date.We aimed to identify, in an agnostic fashion, genes that modify the association between long-term air pollution exposure and annual lung function decline in an adult population-based sample.A two-stage genome-wide interaction study was performed. The discovery (n = 763) and replication (n = 3,896) samples were derived from the multi-center SAPALDIA cohort (Swiss Cohort Study on Air Pollution and Lung Disease in Adults). Annual rate of decline in the forced mid-expiratory flow (FEF25-75%) was the main end point. Multivariate linear regression analyses were used to identify potential multiplicative interactions between genotypes and 11-year cumulative PM10 exposure.We identified a cluster of variants intronic to the CDH13 gene as the only locus with genome-wide significant interactions. The strongest interaction was observed for rs2325934 (p = 8.8 × 10(-10)). Replication of the interaction between this CDH13 variant and cumulative PM10 exposure on annual decline in FEF25-75% was successful (p = 0.008). The interaction was not sensitive to adjustment for smoking or body weight.CDH13 is functionally linked to the adipokine adiponectin, an inflammatory regulator. Future studies need to confirm the interaction and assess how the result relates to previously observed interactions between air pollution and obesity on respiratory function.

SUBMITTER: Imboden M

PROVIDER: S-EPMC4286270 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis.

Imboden Medea M Kumar Ashish A Curjuric Ivan I Adam Martin M Thun Gian Andri GA Haun Margot M Tsai Ming-Yi MY Pons Marco M Bettschart Robert R Turk Alexander A Rochat Thierry T Künzli Nino N Schindler Christian C Kronenberg Florian F Probst-Hensch Nicole M NM

Environmental health perspectives 20140815 1

<h4>Background</h4>Both air pollution and genetic variation have been shown to affect lung function. Their interaction has not been studied on a genome-wide scale to date.<h4>Objectives</h4>We aimed to identify, in an agnostic fashion, genes that modify the association between long-term air pollution exposure and annual lung function decline in an adult population-based sample.<h4>Methods</h4>A two-stage genome-wide interaction study was performed. The discovery (n = 763) and replication (n = 3, ...[more]

PMID: 25127211

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Project description:BackgroundSevere alpha1-antitrypsin (AAT) deficiency is a strong risk factor for COPD. But the impact of gene variants resulting in mild or intermediate AAT deficiency on the longitudinal course of respiratory health remains controversial. There is indication from experimental studies that pro-inflammatory agents like cigarette smoke can interact with these variants and thus increase the risk of adverse respiratory health effects. Therefore, we tested the effect of the presence of a protease inhibitor (Pi) S or Z allele (PiMS and PiMZ) on the change in lung function in different inflammation-exposed subgroups of a large, population-based cohort study.Methodology and principal findingsThe SAPALDIA population includes over 4600 subjects from whom SERPINA1 genotypes for S and Z alleles, spirometry and respiratory symptoms at baseline and after 11 years follow-up, as well as proxies for inflammatory conditions, such as detailed smoking history, obesity and high sensitivity C-reactive protein (hs-CRP), were available. All analyses were performed by applying multivariate regression models. There was no overall unfavourable effect of PiMS or PiMZ genotype on lung function change. We found indication that PiZ heterozygosity interacted with inflammatory stimuli leading to an accelerated decline in measures in use as indices for assessing mild airway obstruction. Obese individuals with genotype PiMM had an average annual decline in the forced mid expiratory flow (?FEF25-75%) of 58.4 ml whereas in obese individuals with PiMZ it amounted to 92.2 ml (p = 0.03). Corresponding numbers for persistent smokers differed even more strongly (66.8 ml (PiMM) vs. 108.2 ml (PiMZ), p = 0.005). Equivalent, but less strong associations were observed for the change in the FEV1/FVC ratio.ConclusionsWe suggest that, in addition to the well established impact of the rare PiZZ genotype, one Z allele may be sufficient to accelerate lung function decline in population subgroups characterized by elevated levels of low grade inflammation.

Dataset Information

Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis.

Publications

Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis.

Similar Datasets

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