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Potential risk modifications of GSTT1, GSTM1 and GSTP1 (glutathione-S-transferases) variants and their association to CAD in patients with type-2 diabetes.
MedLine Citation:
PMID:  21352813     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background Type-2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease (CAD) resulting in high morbidity and mortality. Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) are known for their broad range of detoxification and in the metabolism of xenobiotics. Recent studies revealed the relationship of GSTs variants with T2DM and CAD. In this case-control study we ascertained the association of GSTs variants in association with the development of CAD in patients with T2DM. Methods From Southern part of India, we enrolled 222 T2DM patients, 290 T2DM patients with CAD and 270 healthy controls matched for age, sex and origin. Serum lipid profiles were measured and DNA was extracted from the blood samples. Multiplex PCR for GSTM1/T1 (null polymorphism) and PCR-RFLP for GSTP1 (105 A>G), were performed for genotyping of study participants. Gene frequency and lipid profiles were statistically analyzed for disease association. Results Regression analysis showed that, GSTM1-null genotype is associated with a 2-fold increase (OR= 2.925; 95% CI = 2.078 to 4.119; P< 0.0001) and GSTT1-null genotype is associated with a 3-fold increase (OR= 3.114; 95% CI =2.176 to 4.456; P< 0.0001) to T2DM development. Ile/Val and Val/Val genotypes of GSTP1 also showed a significant risk for T2DM (OR = 1.423, CI = 1.041 to 1.946; P = 0.027 and OR = 1.829, CI = 1.064 to 3.142; P = 0.029). Increased odds ratio showed that GSTT1-null genotype had a moderately higher occurrence in T2DM-CAD patients (OR = 1.918, 95% CI = 1.144 to 3.214; P = 0.014) than T2DM patients without CAD. The level of HDL has significantly decreased in GSTT1-present than in GSTT1-null genotype (43.50±4.10 vs 45.20±3.90; P= 0.004) when compared with control and T2DM patients. However, LDL level showed a significant increase in GSTT1-null than the GSTT1-present genotype (108.70±16.90 vs. 102.20±12.60; P = 0.005). Although the GSTM1-null polymorphism showed no correlation with lipid profiles among T2DM and T2DM with CAD patients, GSTT1-null polymorphism attained a statistical significance for the level of LDL (127±28.20 vs 134±29.10; P=0.039) and triglycerides in T2DM with CAD patients (182.10±21.10 vs 191.20±24.10; P= 0.018). Conclusion Our work concludes that, GSTM1, GSTT1 and GSTP1 variants might contribute in the development of T2DM and GSTT1 variant alone involves in the development of T2DM associated CAD complications in South Indian population.
Authors:
Ramprasath Tharmarajan; Senthil Murugan Ponniah; Ashok Daniel Prabakaran; Gomathi Pannerselvam; Andiappan Rathinavel; Govindan Sadasivam Selvam
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-22
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  -     ISSN:  1090-2104     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
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