Skip to Main content Skip to Navigation
Journal articles

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population.

Abstract : BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter <10 µm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)<0.05). Replication was attempted for SNPs with MAF>10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5×10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7×10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0×10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobacco smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challenging.
Document type :
Journal articles
Complete list of metadatas

Cited literature [60 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00744630
Contributor : Rachel Nadif <>
Submitted on : Tuesday, October 23, 2012 - 3:11:31 PM
Last modification on : Wednesday, September 16, 2020 - 5:06:34 PM
Long-term archiving on: : Saturday, December 17, 2016 - 3:46:13 AM

File

curjuric_po_2012.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Ivan Curjuric, Medea Imboden, Rachel Nadif, Ashish Kumar, Christian Schindler, et al.. Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population.. PLoS ONE, Public Library of Science, 2012, 7 (7), pp.e40175. ⟨10.1371/journal.pone.0040175⟩. ⟨inserm-00744630⟩

Share

Metrics