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Effect of GSTM2-5 polymorphisms in relation to tobacco smoke exposures on lung function growth: a birth cohort study

Effect of GSTM2-5 polymorphisms in relation to tobacco smoke exposures on lung function growth: a birth cohort study
Effect of GSTM2-5 polymorphisms in relation to tobacco smoke exposures on lung function growth: a birth cohort study
Background: genetic variation within GSTM2-5 genes may interfere with detoxification of environmental compounds, thereby having a detrimental effect on lung function following exposures such as tobacco smoke. We aim to investigate the influence of variants and associated methylation in the GSTM gene cluster with changes in lung function growth during adolescence.

Methods: growth in forced expiratory volume (FEV1), forced vital capacity (FVC), and change in FEV1/FVC ratio measures were obtained from children in the Isle of Wight birth cohort at ages 10 and 18. Illumina GoldenGate assays were used to genotype 10 tagging polymorphisms from GSTM2 (rs574344 and rs12024479), GSTM3 (rs1537236, rs7483, and rs10735234), GSTM4 (rs668413, rs560018, and rs506008), and GSTM5 (rs929166 and rs11807) genes. Diplotypes were generated in the software Phase 3.0.2. DNA methylation was measured in over 450,000 CpG sites using the Infinium HumanMethylation450 BeadChip (Illumina 450K) in a subsample of 245 18-year olds from the Isle of Wight birth cohort. Gender, age, in utero smoke exposure, secondhand smoke exposure (SHS), and current smoking status were assessed via questionnaire; smoke exposures were validated with urine cotinine. We used linear mixed models to estimate the effect of GSTM diplotypes on lung function across time and examine interactions with tobacco smoke.

Results: 1,121 (77%) out of 1,456 children had information on lung function at ages 10 or 18. After adjustment for false discovery rate, one diplotype in GSTM3 had a detrimental effect on changes in FEV1 (p=0.03), and another diplotype in GSTM3 reduced FVC (p=0.02) over time. No significant interactions with smoking were identified. SHS significantly modified the relationship between diplotypes and methylation levels in one GSTM2 CpG site; however, this site did not predict lung function outcomes at age 18. Joint effects of GSTM loci and CpG sites located within these loci on adolescent lung growth were detected.

Conclusions: diplotypes within GSTM2-5 genes are associated with lung function growth across adolescence, but do not appear to modify the effect of tobacco smoke exposures on adolescent lung growth. Interactions between DNA methylation and diplotypes should be taken into account to gain further understanding on lung function in adolescence
1471-2466
56
Alexander, Melannie
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Karmaus, Wilfried
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Holloway, John W.
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Zhang, Hongmei
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Roberts, Graham
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Kurukulaaratchy, Ramesh J.
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Arshad, Syed Hasan
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Ewart, Susan
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Alexander, Melannie
b0bd2eb3-cd87-450b-ac3b-091f94fa100c
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Kurukulaaratchy, Ramesh J.
9c7b8105-2892-49f2-8775-54d4961e3e74
Arshad, Syed Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7

Alexander, Melannie, Karmaus, Wilfried, Holloway, John W., Zhang, Hongmei, Roberts, Graham, Kurukulaaratchy, Ramesh J., Arshad, Syed Hasan and Ewart, Susan (2013) Effect of GSTM2-5 polymorphisms in relation to tobacco smoke exposures on lung function growth: a birth cohort study. BMC Pulmonary Medicine, 13 (1), 56. (doi:10.1186/1471-2466-13-56).

Record type: Article

Abstract

Background: genetic variation within GSTM2-5 genes may interfere with detoxification of environmental compounds, thereby having a detrimental effect on lung function following exposures such as tobacco smoke. We aim to investigate the influence of variants and associated methylation in the GSTM gene cluster with changes in lung function growth during adolescence.

Methods: growth in forced expiratory volume (FEV1), forced vital capacity (FVC), and change in FEV1/FVC ratio measures were obtained from children in the Isle of Wight birth cohort at ages 10 and 18. Illumina GoldenGate assays were used to genotype 10 tagging polymorphisms from GSTM2 (rs574344 and rs12024479), GSTM3 (rs1537236, rs7483, and rs10735234), GSTM4 (rs668413, rs560018, and rs506008), and GSTM5 (rs929166 and rs11807) genes. Diplotypes were generated in the software Phase 3.0.2. DNA methylation was measured in over 450,000 CpG sites using the Infinium HumanMethylation450 BeadChip (Illumina 450K) in a subsample of 245 18-year olds from the Isle of Wight birth cohort. Gender, age, in utero smoke exposure, secondhand smoke exposure (SHS), and current smoking status were assessed via questionnaire; smoke exposures were validated with urine cotinine. We used linear mixed models to estimate the effect of GSTM diplotypes on lung function across time and examine interactions with tobacco smoke.

Results: 1,121 (77%) out of 1,456 children had information on lung function at ages 10 or 18. After adjustment for false discovery rate, one diplotype in GSTM3 had a detrimental effect on changes in FEV1 (p=0.03), and another diplotype in GSTM3 reduced FVC (p=0.02) over time. No significant interactions with smoking were identified. SHS significantly modified the relationship between diplotypes and methylation levels in one GSTM2 CpG site; however, this site did not predict lung function outcomes at age 18. Joint effects of GSTM loci and CpG sites located within these loci on adolescent lung growth were detected.

Conclusions: diplotypes within GSTM2-5 genes are associated with lung function growth across adolescence, but do not appear to modify the effect of tobacco smoke exposures on adolescent lung growth. Interactions between DNA methylation and diplotypes should be taken into account to gain further understanding on lung function in adolescence

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e-pub ahead of print date: 3 September 2013
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 356547
URI: http://eprints.soton.ac.uk/id/eprint/356547
ISSN: 1471-2466
PURE UUID: ed78061a-800b-4b0e-961b-11aa9f539b87
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Graham Roberts: ORCID iD orcid.org/0000-0003-2252-1248
ORCID for Ramesh J. Kurukulaaratchy: ORCID iD orcid.org/0000-0002-1588-2400

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Date deposited: 19 Sep 2013 08:46
Last modified: 28 Oct 2023 01:54

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Contributors

Author: Melannie Alexander
Author: Wilfried Karmaus
Author: Hongmei Zhang
Author: Graham Roberts ORCID iD
Author: Susan Ewart

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