ROLE OF THE DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTING ENZYME GENE IN THE PROGRESSION AND THERAPEUTIC RESPONSIVENESS OF IGA NEPHROPATHY

Studies conducted over the last decade demonstrated variable therapeut ic efficacy of angiotensin converting enzyme (ACE) inhibitor on the pr ogression of glomerular diseases, including IgA nephropathy. In this s tudy, among patients with biopsy-proven IgA nephropathy, 53 patients i n whom creatinine clearance had been monitored over 5 yr were recruite d for study, These patients were classified into two groups according to whether or not renal function had declined as determined by the slo pe of creatinine clearance against time: group 1 had stable renal func tion; 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 f or 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 his tory of proteinuria were analyzed as controls. The DD genotype was sig nificantly more frequent in group 2 (43%) than in controls (7%) or gro up 1 patients with stable renal function (16%), 48 wk after ACE inhibi tor administration, proteinuria significantly decreased in patients wi th DD genotype but not in those with ID or II genotypes, The results i ndicate that deletion polymorphism in the ACE gene, particularly the h omozygote DD, is a risk factor for progression to chronic renal failur e in IgA nephropathy. Moreover, this deletion polymorphism predicts th e therapeutic efficacy of ACE inhibition on proteinuria and, potential ly, on progressive deterioration of renal function.