Role of glutathione s-transferase polymorphisms and chronic allograft dysfunction.
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.
Pagliuso
R G
RG
Department of Medicine, São José do Rio Preto Medical School-FAMERP, SP, Brazil.
Abbud-Filho
M
M
Alvarenga
M P S
MP
Ferreira-Baptista
M A S
MA
Biselli
J M
JM
Biselli
P M
PM
Goloni-Bertollo
E M
EM
Pavarino-Bertelli
E C
EC
D003404:Creatinine / Q000097:blood / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D017931:DNA Primers; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D011110:Polymorphism, Genetic; D011507:Proteinuria / Q000453:epidemiology; D013997:Time Factors
D017931:DNA Primers; D007527:Isoenzymes; D003404:Creatinine; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase