Wong K, Summers K, Burstow D, West M
Renin angiotensin system genetic variants and pressure load in cardiac hypertrophy
16th Scientific Meeting of the International Society of Hypertension
ISH Abstract Book (Jun) 16: 1996

57 normals and 53 patients with mild aortic stenosis (gradient greater than 50 mmHg) were studied. LV mass was increased in AoS. The ACE I/D genotype, angiotensinogen T174M genotype and AT1-microsatellite genotype were determined. They had no influence on ventricular wall thickness (WT) in normotensives. In patients with aortic stenosis, however, both angiotensinogen genotype (AGT-MM+MT vs TT) and ACE genotype (DD vs ID + II) were associated with increased WT. Also, the AT1 - B allele was associated with increased WT. The conclusion of the study was, that genetic variants affecting the renin-angiotensin system modify the ventricular response to AoS but have no effect in normals.

Comment: Specifically, this study fits with published data that polymorphisms in the renin-angiotensin system associated with increased activity of this system and increased production of the pressor and growth hormone Ang II cause ventricular hypertrophy. This may only be evident when there is another stimulus to ventricular hypertrophy eg HBP or AoS. However, this study is under-powered (less than 100 subjects) even for a single polymorphism analysis. Multiple comparisons make significance likely by chance and the authors have grouped the genotypes (eg MM + MT). The groupings are inconsistent (MM+MT in one, DI+II) in another. Manipulating the data to look for significance in this way is probably justified and is necessary in small exploratory studies like this - but the results will need to be confirmed or repeated in further, larger studies. Therefore, although tantalizing the data are inadequate to justify the conclusions (Alan Jardine, M.D., Glasgow University, Scotland).

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16th Scientific Meeting of the International Society of Hypertension
H: Pathophysiology : Genetics
H: Pathophysiology : Heart in hypertension