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


OBJECTIVE
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.
Probst-Hensch
Nicole M
NM
Molecular Epidemiology/Cancer Registry, University of Zürich, Zürich, Switzerland. nicole.probst@ifspm.uzh.ch
Imboden
Medea
M
Felber Dietrich
Denise
D
Barthélemy
Jean-Claude
JC
Ackermann-Liebrich
Ursula
U
Berger
Wolfgang
W
Gaspoz
Jean-Michel
JM
Schwartz
Joel
J
D015331:Cohort Studies; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006339:Heart Rate; D006801:Humans; D008297:Male; D009765:Obesity / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D012907:Smoking / Q000235:genetics; D014028:Tobacco Smoke Pollution
D014028:Tobacco Smoke Pollution; D005982:Glutathione Transferase