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 with autosomal dominant polycystic kidney disease (ADPKD). One-hundred, age- and sex-matched subjects with non-ADPKD served as the controls. ACE gene polymorphism was analysed using a GeneAnp kit. Renal size was determined by abdominal CT scan, by adding the longitudinal axis of each 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 distributions of ACE genotypes in ADPKD did not differ from those in controls. The 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 complications including liver cysts and cardiac valvular disease were unrelated to 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 autosomal dominant polycystic kidney disease (ADPKD) has been recently established (1). However, although such gene may be closely linked with phenotypic expressions, a wide spectrum of clinical manifestations in patients with ADPKD is well known (2, 3), suggesting some discrepancy between genotype-phenotype correlation. Progressive enlargement of renal cysts is a cardinal features in ADPKD. A multitude of growth factors have been addressed to be involved in cystogenesis. Amongst, of particular interest is the study that demonstrated renin synthesis by the cyst-lining epithelial cells, suggesting the role of local renin-angiotensin system in cyst cell hyperplasia and cystogenesis (4). Thus, angiotensin converting enzyme (ACE) gene polymorphism, i.e., the insertion or deletion (I/D) of a 287 bp fragment within intron 16, which determines 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.