Gene-load score of the renin-angiotensin-aldosterone system is associated with coronary heart disease in familial hypercholesterolaemia

European Heart Journal
Jeroen B van der NetEric J G Sijbrands

Abstract

Familial hypercholesterolaemia (FH) is characterized by premature coronary heart disease (CHD). However, the incidence of CHD varies considerably among FH patients. Genetic variation in the renin-angiotensin-aldosterone system (RAAS) and the adrenalin/noradrenalin system may be of importance in determining the CHD risk in FH, because of their involvement in CHD. We investigated the association between CHD risk and combined genetic variation in the RAAS and adrenalin/noradrenalin system. In 2190 FH patients, we genotyped six RAAS polymorphisms and five adrenalin/noradrenalin polymorphisms. For each patient, we calculated two gene-load scores by counting the number of risk genotypes within each pathway. Four of the six RAAS polymorphisms and none of the polymorphisms in the adrenalin/noradrenalin system were significantly associated with CHD (P < 0.05). The RAAS gene-load score was significantly associated with CHD (P(linear trend) < 0.001): in patients with a gene-load score of 5 or 6, the CHD risk was 2.3 times as high as in patients with a score of 0 or 1. The gene-load score of the adrenalin/noradrenalin system was not associated with CHD. Genetic variation in the RAAS contributes gene-dose dependently to CHD risk in patients...Continue Reading

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Citations

Oct 15, 2008·Human Molecular Genetics·A Cecile J W Janssens, Cornelia M van Duijn
Apr 4, 2009·Genome Medicine·A Cecile Jw Janssens, Cornelia M van Duijn
Nov 26, 2010·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Simon de DenusMichel White
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