TY - JOUR
T1 - The risk of tendon xanthomas in familial hypercholesterolaemia is influenced by variation in genes of the reverse cholesterol transport pathway and the low-density lipoprotein oxidation pathway
AU - Oosterveer, Daniëlla M.
AU - Versmissen, Jorie
AU - Yazdanpanah, Mojgan
AU - Defesche, Joep C.
AU - Kastelein, John J. P.
AU - Sijbrands, Eric J. G.
PY - 2010
Y1 - 2010
N2 - Aims The presence of tendon xanthomas is a marker of high risk of cardiovascular disease (CVD) among patients with familial hypercholesterolaemia (FH). Therefore, xanthomas and atherosclerosis may result from the same pathophysiological mechanisms. Reverse cholesterol transport (RCT) and low-density lipoprotein (LDL) oxidation are pathophysiological pathways of atherosclerosis, and it is well established that genetic variation in these pathways influences CVD risk. We therefore determined whether genetic variation in these pathways is also associated with the occurrence of tendon xanthomas in FH patients. Methods and results Conclusion Four genetic variants in each pathway were genotyped in 1208 FH patients. We constructed a gene-load score for both pathways. The odds of xanthomas increased with the number of the risk alleles in the RCT pathway (OR 1.21, 95% CI 1.08-1.36, P-trend = 0.0014). Similarly, higher numbers of risk alleles in the LDL oxidation pathway were associated with the presence of xanthomas (OR 1.24, 95% CI 1.08-1.41, P-trend = 0.0015). Conclusion The presence of tendon xanthomas in FH patients is associated with genetic variation in the RCT and LDL oxidation pathways. These results support the hypothesis that xanthomas and atherosclerosis share pathophysiological mechanisms
AB - Aims The presence of tendon xanthomas is a marker of high risk of cardiovascular disease (CVD) among patients with familial hypercholesterolaemia (FH). Therefore, xanthomas and atherosclerosis may result from the same pathophysiological mechanisms. Reverse cholesterol transport (RCT) and low-density lipoprotein (LDL) oxidation are pathophysiological pathways of atherosclerosis, and it is well established that genetic variation in these pathways influences CVD risk. We therefore determined whether genetic variation in these pathways is also associated with the occurrence of tendon xanthomas in FH patients. Methods and results Conclusion Four genetic variants in each pathway were genotyped in 1208 FH patients. We constructed a gene-load score for both pathways. The odds of xanthomas increased with the number of the risk alleles in the RCT pathway (OR 1.21, 95% CI 1.08-1.36, P-trend = 0.0014). Similarly, higher numbers of risk alleles in the LDL oxidation pathway were associated with the presence of xanthomas (OR 1.24, 95% CI 1.08-1.41, P-trend = 0.0015). Conclusion The presence of tendon xanthomas in FH patients is associated with genetic variation in the RCT and LDL oxidation pathways. These results support the hypothesis that xanthomas and atherosclerosis share pathophysiological mechanisms
U2 - https://doi.org/10.1093/eurheartj/ehp538
DO - https://doi.org/10.1093/eurheartj/ehp538
M3 - Article
C2 - 20019024
SN - 0195-668X
VL - 31
SP - 1007
EP - 1012
JO - European Heart journal
JF - European Heart journal
IS - 8
ER -