Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy.

Abstract

Studies conducted over the last decade demonstrated variable therapeutic efficacy of angiotensin converting enzyme (ACE) inhibitor on the progression of glomerular diseases, including IgA nephropathy. In this study, among patients with biopsy-proven IgA nephropathy, 53 patients in whom creatinine clearance had been monitored over 5 yr were recruited for study. These patients were classified into two groups according to whether or not renal function had declined as determined by the slope of creatinine clearance against time: group 1 had stable renal function; group 2 had declining renal function (average: -6.7 +/- 1.3 ml/min/yr). 21 of 53 patients were treated with ACE inhibitor and followed for 48 wk. Gene polymorphism consisting of insertion (I) or deletion (D) of a 287-bp DNA fragment (presumed to be a silencer element) of the ACE gene was determined by PCR. 46 age-matched individuals without history of proteinuria were analyzed as controls. The DD genotype was significantly more frequent in group 2 (43%) than in controls (7%) or group 1 patients with stable renal function (16%). 48 wk after ACE inhibitor administration, proteinuria significantly decreased in patients with DD genotype but not in those with ID or II genotypes. The results indicate that deletion polymorphism in the ACE gene, particularly the homozygote DD, is a risk factor for progression to chronic renal failure in IgA nephropathy. Moreover, this deletion polymorphism predicts the therapeutic efficacy of ACE inhibition on proteinuria and, potentially, on progressive deterioration of renal function.

• Authors: H Yoshida, T Mitarai, T Kawamura, T Kitajima, Y Miyazaki, R Nagasawa, Y Kawaguchi, H Kubo, I Ichikawa, O Sakai
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 96 Issue 5 Pg. 2162-9 (Nov 1995) ISSN: 0021-9738 [Print] United States
• PMID: 7593601 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Peptidyl-Dipeptidase A

Topics

• Adult
• Aged
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Base Sequence
• Female
• Gene Deletion
• Gene Frequency
• Glomerulonephritis, IGA (drug therapy, enzymology, genetics)
• Humans
• Male
• Middle Aged
• Molecular Sequence Data
• Peptidyl-Dipeptidase A (genetics)
• Polymorphism, Genetic