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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=23), only β-blockers (n=26), only angiotensin-converting enzyme inhibitors (ACEi) (n=57) or a combination of treatments (n=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.

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Acknowledgements

This study was supported by Grant (018/98) of the Fondo de Investigaciones Sanitarias (FIS), of the Spanish Health Ministry. Pablo Marín was a recipient of a Grant, FPI98-vs-23-008, from the Department of Culture, Education and Science, Generalitat Valenciana.

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Marin, P., Julve, R., Chaves, F. et al. Polymorphisms of the angiotensinogen gene and the outcome of microalbuminuria in essential hypertension: a 3-year follow-up study. J Hum Hypertens 18, 25–31 (2004). https://doi.org/10.1038/sj.jhh.1001630

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