Polymorphisms of the angiotensinogen gene and the outcome of microalbuminuria in essential hypertension: a 3-year follow-up study

Abstract

Background: The objective of this study was to analyse the relationship of polymorphisms of the angiotensinogen (AGT) gene with the changes in microalbuminuria during 3 years of antihypertensive treatment in a group of young adults with essential hypertension. Methods: Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs and in the absence of diabetes mellitus were included. After the initial evaluation, patients were treated using only nonpharmacological measures (n ¼ 23), only b-blockers (n ¼ 26), only angiotensin-converting enzyme inhibitors (ACEi) (n ¼ 57) or a combination of treatments (n ¼ 25). The office blood pressure, biochemical profile and urinary albumin excretion (UAE) were measured at the beginning and then yearly. The polymorphism A-6G of the AGT gene located in the promoter region was analysed. Results: In total, 131 patients, 35 (27%) microalbuminurics, were included. Although no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose and UAE were observed among genotypes at the initial examination, during the 3 years of antihypertensive treatment the slope values for the DBP, fasting glucose and UAE differed significantly despite no differences in the distribution of treatments being present. The subjects carrying the AA-6 genotype had the largest DBP decrease, but the lowest UAE reduction and the highest slope of glucose. Out of 35 initially microalbuminuric patients, 24 became normoalbuminuric and the lowest reduction rates were observed in subjects who carried the allele A-6. No interaction between the type of treatment and genotype was observed on the changes in UAE, BP or glucose values. In the subset of 57 patients treated with ACEi, the changes in UAE, BP and glucose had the same trend as was observed in the total population. Conclusions: Subjects carrying the AA genotype of the A-6G AGT gene polymorphism are resistant to a reduction of microalbuminuria. Whether this can be attributed to a predisposition to glucose metabolic disturbance or not needs to be confirmed in further studies.

Genetic bases of urinary albumin excretion and related traits in hypertension

“…Although no significant differences in genotypes for either polymorphism were observed between patients with or without microalbuminuria, the A-6G polymorphism seems to influence the risk of new-onset microalbuminuria in a 3-year follow-up study [51]. In this case, the development of microalbuminuria was linked to the changes in fasting glucose and weight [51,52], a previously described association with M235T. In the study performed by Pontremoli et al [53], patients carrying the allele D in ECA, T in AGT and C in AT 1 R have higher early organ damage as compared to carriers of the other alleles of the polymorphisms studied.…”

“…Although no significant differences in genotypes for either polymorphism were observed between patients with or without microalbuminuria, the A-6G polymorphism seems to influence the risk of new-onset microalbuminuria in a 3-year follow-up study [51]. In this case, the development of microalbuminuria was linked to the changes in fasting glucose and weight [51,52], a previously described association with M235T.…”

“…In the AGT gene, the M235T and another polymorphism in strong linkage desequilibrium, A-6G, located in the promoter region have also been studied in a prospective study in young hypertensive patients [51]. Although no significant differences in genotypes for either polymorphism were observed between patients with or without microalbuminuria, the A-6G polymorphism seems to influence the risk of new-onset microalbuminuria in a 3-year follow-up study [51].…”

Microalbuminuria and tubular proteinuria as risk predictors of cardiovascular morbidity and mortality in essential hypertension: final results of a prospective long-term study (MARPLE Study)*

“…Marin et al have very recently reported, that patients with the AA genotype of A-6GAGT genpolymorphism are possibly resistant to reduction of MAU by antihypertensive treatment [34]. It could be speculated that this could be a possible explanation for patients in whom a normalization of MAU in our study could not be achieved.…”

Development of microalbuminuria in essential hypertension

“…The AA-6 genotype of the angiotensinogen gene seemed to influence the outcome of microalbuminuria [68]. Despite a larger decrease in DBP among subjects carrying this genotype as compared to the other genotypes, a lower rate of patients with decreasing microalbuminuria and a higher UAE slope over time were observed in homozygotes for the A-6 allele.…”