Body weight changes and the A-6G polymorphism of the angiotensinogen gene

The objective of the study was to analyze the relationship of polymorphisms of the angiotensinogen gene with changes in body weight during 3 y of antihypertensive treatment, in a group of young adults with essential hypertension.

Essential hypertensives, less than 50 y 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 non-pharmacological measures (n=29), beta-blockers (n=40) or angiotensin-converting enzyme inhibitors (n=66). Resting blood pressure, biochemical profile and body weight at the beginning and yearly were measured. The polymorphism A-6G of the angiotensinogen gene located in the promoter region was analyzed.

One-hundred and thirty-five patients were included. Genotypes of the A-6G polymorphism of the AGT gene were in Hardy-Weinberg equilibrium (AA 34, AG 63, GG 38). No significant differences were observed among genotypes in terms of age, body mass index, body weight, systolic or diastolic blood pressure. No significant differences in the genotype distribution or in the allele frequencies were observed, although the A allele was most frequent among the obese subjects. During the 3 y of antihypertensive treatment, there was a trend to increase weight despite the dietary recommendations. The slopes of body weight over time, adjusted by age and baseline BMI, differed significantly among the homozygote genotypes (P=0.006). The highest were for those with the AA genotype and the lowest for the GG genotype (1.180+/-0.25 and -0.128+/-0.24 kg/y; P=0.0001). The influence of the genotype in the changes on body weight remained significant after considering its interaction with the kind of antihypertensive treatment, although among subjects carrying the AA genotype those treated with ACEi showed the least body weight change. Furthermore, A-6G genotypes had the largest influence on weight changes, accounting for 19% of the variance, when age, sex and initial body mass index were included in the model.

In a group of young adult hypertensive subjects, there was a trend to increase weight despite dietary recommendations. Subjects with the AA genotype were those with the largest weight gain, but this effect was modified by the antihypertensive treatment.