Glutathione-S-transferase genotypes, smoking, and their association with markers of inflammation, hemostasis, and endothelial function: the atherosclerosis risk in communities (ARIC) study.
Recent epidemiologic studies suggest that polymorphisms of glutathione-S-transferases M1 and T1 (GSTM1/GSTT1) modify the effects of cigarette smoking on risk of coronary heart disease (CHD). Since GSTs are able to detoxify numerous toxic compounds and products of oxidative stress, it is possible that GST genotypes may also modify the capacity of smoking to invoke a chronic inflammatory response. A cross-sectional analysis, using a subset of participants (n = 989) in a large (n = 15, 792) biracial cohort, was used to evaluate levels of nine markers of inflammation, hemostasis, and endothelial function by different combinations of GST genotypes and cigarette smoking status. Participants with the GSTM1 null (GSTM1-0) genotype and > or = 20 pack-years of smoking had the highest mean levels of CRP, fibrinogen, von Willebrand factor, ICAM-1, and VCAM-1 and lowest mean levels of albumin compared to other combinations of genotype and smoking. However, a formal test for interaction between GSTM1 genotype and smoking was statistically significant only for albumin. By contrast, participants who had the functional GSTT1 genotype (GSTT1-1) and smoked > or = 20 pack-years had the highest mean levels of only CRP and fibrinogen. The results of this study provide some limited evidence that GSTM1 and GSTT1 polymorphisms modify the effect of smoking on inflammation, hemostasis, and endothelial function.
Miller
Eric A
EA
Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
Pankow
James S
JS
Millikan
Robert C
RC
Bray
Molly S
MS
Ballantyne
Christie M
CM
Bell
Douglas A
DA
Heiss
Gerardo
G
Li
Rongling
R
D015331:Cohort Studies; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D015994:Incidence; D018836:Inflammation Mediators / Q000032:analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D012111:Residence Characteristics; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology*; D014481:United States / Q000453:epidemiology
D005819:Genetic Markers; D005982:Glutathione Transferase; D018836:Inflammation Mediators; C413545:glutathione S-transferase T1