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Glutathione S-transferase polymorphisms, passive smoking, obesity, and heart rate variability in nonsmokers


Probst-Hensch, N M; Imboden, M; Felber Dietrich, D; Barthélémy, Jean Claude; Ackermann-Liebrich, U; Berger, W; Gaspoz, Jean-Michel; Schwartz, J (2008). Glutathione S-transferase polymorphisms, passive smoking, obesity, and heart rate variability in nonsmokers. Environmental Health Perspectives, 116(11):1494-1499.

Abstract

BACKGROUND: Disturbances of heart rate variability (HRV) may represent one pathway by which second-hand smoke (SHS) and air pollutants affect cardiovascular morbidity and mortality. The mechanisms are poorly understood. OBJECTIVES: We investigated the hypothesis that oxidative stress alters cardiac autonomic control. We studied the association of polymorphisms in oxidant-scavenging glutathione S-transferase (GST) genes and their interactions with SHS and obesity with HRV. METHODS: A total of 1,133 nonsmokers > 50 years of age from a population-based Swiss cohort underwent ambulatory 24-hr electrocardiogram monitoring and reported on lifestyle and medical history. We genotyped GSTM1 and GSTT1 gene deletions and a GSTP1 (Ile105Val) single nucleotide polymorphism and analyzed genotype-HRV associations by multiple linear regressions. RESULTS: Homozygous GSTT1 null genotypes exhibited an average 10% decrease in total power (TP) and low-frequency-domain HRV parameters. All three polymorphisms modified the cross-sectional associations of HRV with SHS and obesity. Homozygous GSTM1 null genotypes with > 2 hr/day of SHS exposure exhibited a 26% lower TP [95% confidence interval (CI), 11 to 39%], versus a reduction of -5% (95% CI, -22 to 17%) in subjects with the gene and the same SHS exposure compared with GSTM1 carriers without SHS exposure. Similarly, obese GSTM1 null genotypes had, on average, a 22% (95% CI, 12 to 31%) lower TP, whereas with the gene present obesity was associated with only a 3% decline (95% CI, -15% to 10%) compared with nonobese GSTM1 carriers. CONCLUSIONS: GST deficiency is associated with significant HRV alterations in the general population. Its interaction with SHS and obesity in reducing HRV is consistent with an impact of oxidative stress on the autonomous nervous system.

Abstract

BACKGROUND: Disturbances of heart rate variability (HRV) may represent one pathway by which second-hand smoke (SHS) and air pollutants affect cardiovascular morbidity and mortality. The mechanisms are poorly understood. OBJECTIVES: We investigated the hypothesis that oxidative stress alters cardiac autonomic control. We studied the association of polymorphisms in oxidant-scavenging glutathione S-transferase (GST) genes and their interactions with SHS and obesity with HRV. METHODS: A total of 1,133 nonsmokers > 50 years of age from a population-based Swiss cohort underwent ambulatory 24-hr electrocardiogram monitoring and reported on lifestyle and medical history. We genotyped GSTM1 and GSTT1 gene deletions and a GSTP1 (Ile105Val) single nucleotide polymorphism and analyzed genotype-HRV associations by multiple linear regressions. RESULTS: Homozygous GSTT1 null genotypes exhibited an average 10% decrease in total power (TP) and low-frequency-domain HRV parameters. All three polymorphisms modified the cross-sectional associations of HRV with SHS and obesity. Homozygous GSTM1 null genotypes with > 2 hr/day of SHS exposure exhibited a 26% lower TP [95% confidence interval (CI), 11 to 39%], versus a reduction of -5% (95% CI, -22 to 17%) in subjects with the gene and the same SHS exposure compared with GSTM1 carriers without SHS exposure. Similarly, obese GSTM1 null genotypes had, on average, a 22% (95% CI, 12 to 31%) lower TP, whereas with the gene present obesity was associated with only a 3% decline (95% CI, -15% to 10%) compared with nonobese GSTM1 carriers. CONCLUSIONS: GST deficiency is associated with significant HRV alterations in the general population. Its interaction with SHS and obesity in reducing HRV is consistent with an impact of oxidative stress on the autonomous nervous system.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > Institute of Medical Molecular Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:24 Feb 2009 13:02
Last Modified:06 Dec 2017 18:38
Publisher:National Institute of Environmental Health Sciences
ISSN:0091-6765
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1289/ehp.11402
PubMed ID:19057702

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