ASSOCIATION BETWEEN ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM AND CLINICAL-FEATURES IN AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE

We investigated the association between angiotensin converting enzyme (ACE) gene polymorphism and clinical manifestations in 47 patients wit h autosomal dominant polycystic kidney disease (ADPKD). One-hundred, a ge- and sex-matched subjects with non-ADPKD served as the controls. AC E gene polymorphism was analysed using a GeneAnp kit. Renal size was d etermined by abdominal CT scan, by adding the longitudinal axis of eac h kidney. Incidence of extrarenal complication was also examined. Out of 47 patients, 24 patients (51%) were II, 18 (38%) ID and 5 (11%) DD type. The frequencies of the I and D alleles as well as the distributi ons of ACE genotypes in ADPKD did not differ from those in controls. T he number of patients undertaking renal replacement therapy was 11 in II (46%), 6 (33%) in ID and 2 (40%) in DD genotype, respectively, that was not significantly different among the groups. The mean age of the initiation of renal replacement therapy did not vary among the three genotypes. The slopes of 1/serum creatinine did not differ between II and ID genotypes, whose initial serum creatinine levels ranged from 1. 5 to 2.5 mg/dl. Renal size, blood pressure, and extrarenal complicatio ns including liver cysts and cardiac valvular disease were unrelated t o the ACE genotypes. The present data suggested the irrelevance of ACE gene polymorphism in clinical manifestations in patients with ADPKD. The structure of the responsible gene and its transcript protein for a utosomal dominant polycystic kidney disease (ADPKD) has been recently established (1). However, although such gene may be closely linked wit h phenotypic expressions, a wide spectrum of clinical manifestations i n patients with ADPKD is well known (2, 3), suggesting some discrepanc y between genotype-phenotype correlation. Progressive enlargement of r enal cysts is a cardinal features in ADPKD. A multitude of growth fact ors have been addressed to be involved in cystogenesis. Amongst, of pa rticular interest is the study that demonstrated renin synthesis by th e cyst-lining epithelial cells, suggesting the role of local renin-ang iotensin system in cyst cell hyperplasia and cystogenesis (4). Thus, a ngiotensin converting enzyme (ACE) gene polymorphism, i.e., the insert ion or deletion (I/D) of a 287 bp fragment within intron 16, which det ermines the tissue level of ACE activity (5), may modify the clinical manifestations in this hereditary renal disease, To unveil this issue, we undertook this study in Japanese ADPKD patients.