alpha-Adducin and angiotensin-converting enzyme polymorphisms in hypertension : evidence for a joint influence on albuminuria

BACKGROUND: A single-nucleotide polymorphism (Gly460Trp) within the alpha-adducin gene (ADD1) may influence several renal phenotypes, including salt sensitivity, susceptibility to renal failure, the renal haemodynamics and confer a worse cardiovascular risks profile. However, its relationship with microalbuminuria, a marker of early renal and cardiovascular damage and an independent predictor of morbid events in hypertension, is unknown. For this reason, we related the ADD1 genetic polymorphism to urine albumin levels and other clinical variables in essential hypertensive men. The angiotensin-converting enzyme (ACE) insertion/deletion (ID) polymorphism was also evaluated because of its interactive potential with the ADD1 genotype. METHODS: Albuminuria (three overnight collections), echocardiographic left ventricular mass index, blood pressure, body mass index, renal function, glucose and lipids were measured in 238 genetically unrelated, never treated, uncomplicated Caucasian essential hypertensive men. Polymerase chain reaction or a 5' nuclease assay were used to characterize the ACE ID and ADD1 Gly460Trp variants, respectively. RESULTS: Microalbuminuria (albuminuria >or= 15 microg/min) was more frequent in patients with the ACE DD variant, but only in those with a ADD1 Gly460Gly background. In contrast, urine albumin did not differ by ACE ID genotype in the presence of mutated ADD1 Trp alleles. ADD1 polymorphisms per se were not associated with albuminuria. Cardiovascular, renal, metabolic parameters were homogeneously distributed among different genetic backgrounds. CONCLUSIONS: ACE DD and ADD1 Gly460Gly polymorphisms may jointly influence albuminuria in hypertensive men, 460Gly homozygosis facilitating or, possibly, the 460Trp allele mitigating the noxious renal impact of the ACE DD genotype. The data highlight further the complex pathophysiological implications of microalbuminuria in hypertension.