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


OBJECTIVE
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.
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute SwissTPH, Basel, Switzerland.
Ivan
I
Curjuric
Medea
M
Imboden
Rachel
R
Nadif
Ashish
A
Kumar
Christian
C
Schindler
Margot
M
Haun
Florian
F
Kronenberg
Nino
N
Künzli
Harish
H
Phuleria
Dirkje S
DS
Postma
Erich W
EW
Russi
Thierry
T
Rochat
Florence
F
Demenais
Nicole M
NM
Probst-Hensch
D000328:Adult; D000368:Aged; D000397:Air Pollution / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D052638:Particulate Matter / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide; D012129:Respiratory Function Tests; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires
D052638:Particulate Matter