A common variant in the glutathione S transferase gene is associated with elevated markers of inflammation and lipid peroxidation in subjects with diabetes mellitus.
BACKGROUND
Glutathione S transferases (GST) are enzymes responsible for the metabolism of numerous xenobiotics and play a major cellular antioxidant role. Our aim was firstly, to examine the association between the GST M1/GST mu-1 (GSTM1) and GST T1/GST theta-1 (GSTT1) gene variants with markers of oxidative stress and inflammation in diabetic patients, and secondly to examine the association and potential interaction between these variants and cigarette smoking.


METHODS
Seven hundred and seventy-three Caucasian subjects with diabetes and 2592 Caucasian non-diabetic subjects were successfully genotyped. Plasma total antioxidant status, C-reactive protein (CRP), oxidized-LDL (Ox-LDL) and LDL-mean/peak particle diameter were recorded in the diabetes sample.


RESULTS
No association was seen between genotype and cardiovascular disease (CVD) risk. In the diabetic subjects, GSTT1-1 compared to GSTT1-0 subjects had significantly higher CRP (p=0.001), Ox-LDL (p=0.004) and smaller LDL particles (p=0.01). In subjects without CVD, there was a significant interaction between the GSTT1-1 variant and smoking in determining Ox-LDL (p=0.04). Furthermore, CVD risk was higher in smokers compared to non-smokers with GSTT1-1. No significant associations were observed by GSTM1. Within the non-diabetic sample, no association was observed between genotype and prospective coronary heart disease (CHD) risk. Of note, the frequency of the GSTT1-1 variant was significantly lower in the diabetes subjects compared to the non-diabetic sample (p=0.01).


CONCLUSIONS
This study demonstrates an association between the GSTT1-1 variant and markers of inflammation and lipid peroxidation. Furthermore this variant interacts with smoking to increase lipid peroxidation.
Hayek
Tony
T
Lipid Research Unit, Rambam Medical Center, The Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Stephens
Jeffrey W
JW
Hubbart
Christina S
CS
Acharya
Jayshree
J
Caslake
Muriel J
MJ
Hawe
Emma
E
Miller
George J
GJ
Hurel
Steven J
SJ
Humphries
Steve E
SE
D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000235:genetics; D004247:DNA / Q000235:genetics*; D003920:Diabetes Mellitus / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015227:Lipid Peroxidation / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors
D000975:Antioxidants; D015415:Biomarkers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein; D004247:DNA; D005982:Glutathione Transferase