Article
The G1675A Gene Polymorphism of the AT2-Receptor Gene influences Cardiac Structural Response to Antihypertensive Therapy
Der G1675A Genpolymorphismus des AT2-Rezeptor Gens beeinflußt den Effekt einer antihypertensiven Therapie auf die kardiale Struktur
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Published: | November 11, 2004 |
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Outline
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Introduction
In vitro, the angiotensin II type 2 receptor (AT2-R) exerts antiproliferative effects in the cardiovascular system. Moreover, the G1675A gene polymorphism of the AT2-R has been shown to influence left ventricular structure in essential hypertensive subjects. We hypothesized that this gene polymorphism may also alter the cardiac structural response to antihypertensive therapy, in particular to agents interfering with the renin-angiotensin-system.
Methods
In the Cardiovascular Irbesartan Project (CVIP), a double blind randomized clinical study, patients with mild-to-moderate essential hypertension and early target organ damage as evidenced by an increased intima media thickness (IMT) of the common carotid artery (0.8-1.5 mm) were treated with either irbesartan or atenolol for 18 months. The G1675A genotype of the AT2-R gene was determined by a 5' nuclease allelic discrimination assay using real-time PCR in 112 subjects.
Results
At baseline, blood pressure and left ventricular mass index (LVMI) were similar between genotypes. In addition, after 6 and after 18 months, blood pressure control was similar between genotypes. However, G allele carriers (males with G genotype and females with GG or GA genotype, n=62) showed an increase in LVMI while hemizygous males and females with the AA genotype (n=50) showed a decrease in LVMI (+2.5±20.4 vs -8.8±25.0 g/m2, p=0.02 after 6 months and +6.6±26.3 vs -11.4±21.9 g/m2,, p=0.002 after 18 months). These differences were also observed in both treatment subgroups to a similar extent.
Conclusion
The A allele of the G1675A polymorphism of the AT2-R was associated with a favorable response of cardiac structure to antihypertensive therapy, regardless of the type of treatment.