ACE gene I/D polymorphism and the presence of renal failure or hypertension in autosomal dominant polycystic kidney disease (ADPKD)

Abstract

Sir,Epidemiological data have suggested that interactionsbetween multiple genetic and environmental factors areinvolved in the process of progressive renal damage in thecourse of various kidney diseases, including autosomalpolycystic kidney disease [1–4].Recently, we read with interest the results of a meta-analysis of studies examining the association betweenangiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and the presence of end-stagerenal disease (ESRD) in patients with ADPKD [5]. Based onthe analysis of combined data from 13 reports, Pereira et al.[5] found no proof for the involvement of ACE gene I/Dmarker in the development of ESRD or hypertension inADPKD patients.Inspired by this report, we looked into ACE I/D genotypesobtained in a small sample of 105 Caucasian ADPKDpatients [58 women and 47 men, median age 43 years(25–75%: 35–54 years)], of whom 42 presented renal failure(S-creatinine 130mmol/l), with median serum creatinine of432mmol/l (25–75%: 192–780mmol/l). Seventy patients werehypertensive (systolic blood pressure 140mmHg and/ordiastolic blood pressure 90mmHg, or antihypertensivetreatment). There were no significant differences in I/Dgenotype distributions between ADPKD patients, with andwithout renal failure. Frequencies of D/D, I/D and I/Igenotypes among patients with renal failure were 33, 57,10%, respectively, and 33, 49 and 18% in those with normalS-creatinine levels. In hypertensive patients, D/D, I/D andI/I genotype frequencies were 34, 57 and 9%, while innormotensives, they were 34, 43 and 23%, respectively.Genotype distribution obtained in 130 healthy controls was37, 37 and 16% (D/D, I/D and I/I, respectively). We foundno differences in serum ACE levels between ADPKDpatients with and without renal failure, or in patients withhypertension vs normotensives. However, ACE levels werehighest among carriers of the DD genotype, and lowest in theI/I group, with heterozygotes presenting intermediate levels.In summary, our data obtained in a small sample ofADPKD patients failed to show an association between theACE gene polymorphism and the presence of renal failure orhypertension, and can be added to further meta-analyses ofADPKD patients.