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The D‐allele of the ACE gene polymorphism predicts a stronger antiproteinuric response to ACE inhibitors
Author(s) -
VLEMING Louis J,
VAN KOOTEN Cees,
VAN DIJK Marjan,
HOLLANDER Daan AMJ,
PAAPE Marion E,
WESTENDORP Rudi GJ,
ES Leendert A
Publication year - 1998
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1046/j.1440-1797.1998.d01-30.x
Subject(s) - medicine , microalbuminuria , proteinuria , angiotensin converting enzyme , genotype , endocrinology , ace inhibitor , genotyping , allele , diabetes mellitus , allele frequency , genetics , kidney , gene , biology , blood pressure
SUMMARY: Angiotensin converting enzyme (ACE) inhibitors have additional renoprotective effects over other antihypertensive drugs in retarding the development and progression of diabetic and non‐diabetic nephropathies. This additional beneficial effect has been attributed to their antiproteinuric action. However, individual antiproteinuric responses to ACE inhibitors vary considerably. the mechanism underlying the variable response is unresolved. the role of the insertion/deletion (I/D) polymorphism of the ACE gene in this response was examined. the case series consisted of 96 patients (69 males, median age 46.5 years) on ACE inhibitors with an initial proteinuria in excess of 1.0 g/24h. A control series consisted of 103 patients (43 males, median age 40 years) with autosomal polycystic kidney disease. A second control series consisted of 82 patients (52 males, median age 39 years) with a diagnosis of insulin‐dependent diabetes mellitus (IDDM) without microalbuminuria after more than 15 years of IDDM. Angiotensin converting enzyme genotyping was performed by polymerase chain reaction (PCR) analysis of chromosomal DNA. the ACE genotype distribution (DD 44%, ID 28%, II 28%) in the case series was not in accordance with the Hardy‐Weinberg equilibrium (χ 2 = 17.2, P <0.001), whereas it was in both control series. the difference in ACE genotype distribution between the case series and both control series combined was significant as a result of an overrepresentation of patients with the DD genotype (χ 2 =9.2, P =0.01). the allele frequencies were compared in patients with a reduction of proteinuria above and below the median value of 45%. the antiproteinuric effectiveness of ACEI therapy in the whole group was greater in the presence of the D‐allele (OR 1.6, 95% CI 0.9‐2.9). the effect of the D‐allele was more pronounced in the subgroup of patients with an initial proteinuria in the non‐nephrotic range (relative risk 2.8, 95%CI 1.0‐8.0) and in patients not receiving diuretics (relative risk 2.3, 95% CI 1.1–4.5). In conclusion, the DD genotype seems to predispose the development of proteinuria in the presence of a kidney disorder. the presence of the D‐allele predicts a stronger antiproteinuric efficacy of ACE inhibitor therapy in patients with an initial proteinuria in the non‐nephrotic range and in the patients not requiring comedication with diuretics.