Insertion/Deletion polymorphism of Angiotensin-converting enzyme as a risk factor for chronic allograft nephropathy.
Angiotensin-converting enzyme (ACE) inhibitor therapy is widely used to treat chronic allograft nephropathy (CAN), which suggests a possible role of the renin-angiotensin system in the pathologic mechanism of the disease. The objective of this study was to investigate the possible link between CAN and ACE. The ACE insertion/deletion polymorphism and the amount and activity of ACE were determined in cadaver kidney recipients with CAN (n = 38) or normal renal function (n = 34). The DD genotype was observed significantly more frequently in the CAN group compared with the group with normal renal function. Moreover, the DD genotype was associated with a higher serum ACE concentration and greater serum ACE activity, compared with II genotype homozygotes. The insertion/deletion polymorphism of ACE affects ACE expression and activity in serum, and, therefore, may have an important role in the pathogenesis of CAN. These findings suggest that determination of the ACE genotype may be useful in identifying patients at high risk. In particular, the DD genotype may be considered an indication for ACE inhibitor therapy.
Fedor
R
R
Department of Surgery, Transplantation Center, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. f_roli@yahoo.com
Asztalos
L
L
Löcsey
L
L
Szabó
L
L
Mányiné
I S
IS
Fagyas
M
M
Lizanecz
E
E
Tóth
A
A
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D002102:Cadaver; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004251:DNA Transposable Elements; D005260:Female; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D007674:Kidney Diseases / Q000235:genetics*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion; D014019:Tissue Donors; D014184:Transplantation, Homologous
D000806:Angiotensin-Converting Enzyme Inhibitors; D004251:DNA Transposable Elements; D008055:Lipids; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A