TY - JOUR
T1 - Association of RANK/RANKL/OPG gene polymorphisms with risk of peripheral arterial disease (PAD) and critical limb ischemia in the general Italian population
AU - Biscetti, Federico
AU - Straface, G.
AU - Angelini, F.
AU - Pitocco, Dario
AU - Landolfi, Raffaele
AU - Flex, Andrea
PY - 2017
Y1 - 2017
N2 - Background Peripheral arterial disease (PAD) is an important determinant of the excessive morbidity and mortality in atherosclerotic patients, especially in patients with critical limb ischemia (CLI). Several studies recently conducted have demonstrated that the RANK/RANKL/OPG system plays an important role in the metabolism of the bone and in vascular pathology, including atherogenesis and arterial calcification and is involved in plaque instability and rupture by inducing plaque calcification. Aim and methods The aim of the present study to evaluate whether the rs3134069, the rs2073617, and the rs2073618 polymorphisms of the OPG gene, the rs9533156 and the rs2277438 gene variants of the RANKL gene and the rs1805034 gene polymorphism of the RANK gene are associated with presence and severity of PAD in general Italian population. Our study included 1221 patients (523 with PAD and 698 controls without PAD). Results We found that the rs3134069, the rs2073617, and the rs2073618 polymorphisms of the OPG gene, the rs9533156 gene variants of the RANKL gene and the rs1805034 gene polymorphism of the RANK gene were significantly and independently associated with PAD. We also found that these five polymorphisms act synergistically in patients with PAD and are associated with different levels of risk for PAD and CLI, depending on the number of high-risk genotypes carried concomitantly by a given individual. Discussion Genetic variations of rs3134069, rs2073617, and rs2073618 on the OPG gene, rs9533156 on the RANKL gene and rs1805034 on the RANK gene are associated with the risk to develop PAD and these five gene polymorphisms act synergistically in patients with PAD and are associated with different risk for PAD.
AB - Background Peripheral arterial disease (PAD) is an important determinant of the excessive morbidity and mortality in atherosclerotic patients, especially in patients with critical limb ischemia (CLI). Several studies recently conducted have demonstrated that the RANK/RANKL/OPG system plays an important role in the metabolism of the bone and in vascular pathology, including atherogenesis and arterial calcification and is involved in plaque instability and rupture by inducing plaque calcification. Aim and methods The aim of the present study to evaluate whether the rs3134069, the rs2073617, and the rs2073618 polymorphisms of the OPG gene, the rs9533156 and the rs2277438 gene variants of the RANKL gene and the rs1805034 gene polymorphism of the RANK gene are associated with presence and severity of PAD in general Italian population. Our study included 1221 patients (523 with PAD and 698 controls without PAD). Results We found that the rs3134069, the rs2073617, and the rs2073618 polymorphisms of the OPG gene, the rs9533156 gene variants of the RANKL gene and the rs1805034 gene polymorphism of the RANK gene were significantly and independently associated with PAD. We also found that these five polymorphisms act synergistically in patients with PAD and are associated with different levels of risk for PAD and CLI, depending on the number of high-risk genotypes carried concomitantly by a given individual. Discussion Genetic variations of rs3134069, rs2073617, and rs2073618 on the OPG gene, rs9533156 on the RANKL gene and rs1805034 on the RANK gene are associated with the risk to develop PAD and these five gene polymorphisms act synergistically in patients with PAD and are associated with different risk for PAD.
KW - Atherosclerosis
KW - Critical limb ischemia
KW - RANK and RANKL gene polymorphisms
KW - Peripheral arterial disease
KW - OPG
KW - Atherosclerosis
KW - Critical limb ischemia
KW - RANK and RANKL gene polymorphisms
KW - Peripheral arterial disease
KW - OPG
UR - http://hdl.handle.net/10807/305663
U2 - 10.1016/j.mgene.2016.12.001
DO - 10.1016/j.mgene.2016.12.001
M3 - Article
SN - 2214-5400
VL - 11
SP - 85
EP - 90
JO - Meta Gene
JF - Meta Gene
ER -