Dataset Information

GST-omega genes interact with environmental tobacco smoke on adult level of lung function.

ABSTRACT: BACKGROUND: Lung growth in utero and lung function loss during adulthood can be affected by exposure to environmental tobacco smoke (ETS). The underlying mechanisms have not been fully elucidated. Both ETS exposure and single nucleotide polymorphisms (SNPs) in Glutathione S-Transferase (GST) Omega genes have been associated with the level of lung function. This study aimed to assess if GSTO SNPs interact with ETS exposure in utero and during adulthood on the level of lung function during adulthood. METHODS: We used cross-sectional data of 8,128 genotyped participants from the LifeLines cohort study. Linear regression models (adjusted for age, sex, height, weight, current smoking, ex-smoking and packyears smoked) were used to analyze the associations between in utero, daily and workplace ETS exposure, GSTO SNPs, the interaction between ETS and GSTOs, and level of lung function (FEV(1), FEV(1)/FVC). Since the interactions between ETS and GSTOs may be modified by active tobacco smoking we additionally assessed associations in never and ever smokers separately. A second sample of 5,308 genotyped LifeLines participants was used to verify our initial findings. RESULTS: Daily and workplace ETS exposure was associated with significantly lower FEV(1)levels. GSTO SNPs (recessive model) interacted with in utero ETS and were associated with higher levels of FEV(1), whereas the interactions with daily and workplace ETS exposure were associated with lower levels of FEV(1), effects being more pronounced in never smokers. The interaction of GSTO2 SNP rs156697 with in utero ETS associated with a higher level of FEV(1) was significantly replicated in the second sample. Overall, the directions of the interactions of in utero and workplace ETS exposure with the SNPs found in the second (verification) sample were in line with the first sample. CONCLUSIONS: GSTO genotypes interact with in utero and adulthood ETS exposure on adult lung function level, but in opposite directions.

SUBMITTER: de Jong K

PROVIDER: S-EPMC3751364 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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GST-omega genes interact with environmental tobacco smoke on adult level of lung function.

de Jong Kim K Boezen H Marike HM Hacken Nick H T ten NH Postma Dirkje S DS Vonk Judith M JM

Respiratory research 20130809

<h4>Background</h4>Lung growth in utero and lung function loss during adulthood can be affected by exposure to environmental tobacco smoke (ETS). The underlying mechanisms have not been fully elucidated. Both ETS exposure and single nucleotide polymorphisms (SNPs) in Glutathione S-Transferase (GST) Omega genes have been associated with the level of lung function. This study aimed to assess if GSTO SNPs interact with ETS exposure in utero and during adulthood on the level of lung function during ...[more]

PMID: 23937118

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Project description: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.

Project description:The developing fetus is especially vulnerable to environmental toxicants, including tobacco constituents. The aim of this study was to assess the impact of environmental tobacco smoke (ETS) exposure during pregnancy on child neurodevelopment within the first two years of life. The study population consisted of 461 non-smoking pregnant women (saliva cotinine level <10 ng/mL). Maternal passive smoking was assessed based on the cotinine level in saliva analyzed by the use of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS) and by questionnaire data. The cotinine cut-off value for passive smoking was established at 1.5 ng/mL (sensitivity 63%, specificity 71%). Psychomotor development was assessed in children at the age of one- and two-years using the Bayley Scales of Infant and Toddler Development. Approximately 30% of the women were exposed to ETS during pregnancy. The multivariate linear regression model indicated that ETS exposure in the 1st and the 2nd trimesters of pregnancy were associated with decreasing child language functions at the age of one (? = -3.0, p = 0.03, and ? = -4.1, p = 0.008, respectively), and two years (? = -3.8, p = 0.05, and ? = -6.3, p = 0.005, respectively). A negative association was found for cotinine level ?1.5 ng/mL in the 2nd trimester of pregnancy and child cognition at the age of 2 (? = -4.6, p = 0.05), as well as cotinine levels ?1.5 ng/mL in all trimesters of pregnancy and child motor abilities at two years of age (? = -3.9, p = 0.06, ? = -5.3, p = 0.02, and ? = -4.2, p = 0.05, for the 1st, the 2nd, and the 3rd trimester of pregnancy, respectively; for the 1st trimester the effect was of borderline statistical significance). This study confirmed that ETS exposure during pregnancy can have a negative impact on child psychomotor development within the first two years of life and underscore the importance of public health interventions aiming at reducing this exposure.

Dataset Information

GST-omega genes interact with environmental tobacco smoke on adult level of lung function.

Publications

GST-omega genes interact with environmental tobacco smoke on adult level of lung function.

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