Role of glutathione s-transferase polymorphisms and chronic allograft dysfunction.

Abstract

Polymorphisms within genes encoding glutathione S-transferases (GSTs) may affect responses against damage induced by oxidative stress and therefore play a role to prevent chronic allograft dysfunction (CAD). In the present study, we estimated the frequencies of GSTM1- and GSTT1-null genotypes among 227 renal transplant recipients seeking to establish an association with CAD. Patients persistently displaying serum creatinine (sCr) values < or = 1.5 mg/dL, measured creatinine clearances (CLcr) > or = 50 mL/min/1.73 m(2), and 24-hour proteinuria < or = 500 mg were classified as normal graft function (NF; n = 107). In contrast, the CAD group (n = 120) presented sCr > 1.5 mg/dL, CLcr < 50 mL/min/1.73 m(2), and proteinuria > 500 mg. The GSTM1 and GSTT1 polymorphisms were evaluated by the multiplex polymerase chain reaction. The frequencies of GSTT1-null genotypes in NF and CAD cohorts were 15% and 24.2%, respectively (P = .057), while GSTM1-null genotypes in the same groups of patients were 44% and 46.7% (P = .389). A combination of null genotypes for GSTT1 and GSTM1 was observed in 9.2% of patients with CAD and in 5.6% of those with NF (P = .449). This study did not show an association of either GSTT1- and GSTM1-null genotypes with CAD. It is likely that development and progression of CAD are determined by a combination of complex genetic traits resulting from the interplay of several genes rather than a single gene.

• Authors: R G Pagliuso, M Abbud-Filho, M P S Alvarenga, M A S Ferreira-Baptista, J M Biselli, P M Biselli, E M Goloni-Bertollo, E C Pavarino-Bertelli
• Journal: Transplantation proceedings (Transplant Proc) Vol. 40 Issue 3 Pg. 743-5 (Apr 2008) ISSN: 0041-1345 [Print] United States
• PMID: 18455004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Isoenzymes
• Creatinine
• Cytochrome P-450 CYP1A1
• Glutathione Transferase

Topics

• Creatinine (blood, metabolism)
• Cytochrome P-450 CYP1A1 (genetics)
• DNA Primers
• Follow-Up Studies
• Genotype
• Glutathione Transferase (genetics)
• Humans
• Isoenzymes (genetics)
• Kidney Transplantation (pathology, physiology)
• Polymorphism, Genetic
• Proteinuria (epidemiology)
• Time Factors