RGD Reference Report - A common variant in the glutathione S transferase gene is associated with elevated markers of inflammation and lipid peroxidation in subjects with diabetes mellitus. - Rat Genome Database

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A common variant in the glutathione S transferase gene is associated with elevated markers of inflammation and lipid peroxidation in subjects with diabetes mellitus.

Authors: Hayek, T  Stephens, JW  Hubbart, CS  Acharya, J  Caslake, MJ  Hawe, E  Miller, GJ  Hurel, SJ  Humphries, SE 
Citation: Hayek T, etal., Atherosclerosis. 2006 Feb;184(2):404-12. Epub 2005 Jul 5.
RGD ID: 5490997
Pubmed: PMID:16002077   (View Abstract at PubMed)
DOI: DOI:10.1016/j.atherosclerosis.2005.05.017   (Journal Full-text)

INTRODUCTION: 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.




  
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Term
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Evidence
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Original Reference(s)
GSTT1Humandiabetes mellitus susceptibilityIAGP DNA:deletion: :RGD 
Gstt1Ratdiabetes mellitus susceptibilityISOGSTT1 (Homo sapiens)DNA:deletion: :RGD 
Gstt1Mousediabetes mellitus susceptibilityISOGSTT1 (Homo sapiens)DNA:deletion: :RGD 


Genes (Rattus norvegicus)
Gstt1  (glutathione S-transferase theta 1)

Genes (Mus musculus)
Gstt1  (glutathione S-transferase, theta 1)

Genes (Homo sapiens)
GSTT1  (glutathione S-transferase theta 1)