title: A single nucleotide polymorphism in the promoter region of the human gene for osteoprotegerin is related to vascular morphology and function.
abstract: Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor receptor family, and has previously been shown to regulate bone mass by inhibiting osteoclast differentiation and activation. Recent evidence indicates that OPG also plays a role in the vascular system, since ablation of the OPG gene in mice results in calcification of the aorta and renal arteries, and association has been found between serum levels of OPG and cardiovascular mortality. This study presents a novel single nucleotide polymorphism, a T/C transition located 129 bp upstream the TATA-box of the human OPG gene, detected by sequence analysis. The OPG genotype was determined by restriction fragment length polymorphism in a cohort consisting of 59 healthy subjects. The intima-media thickness (IMT) in the common carotid artery and maximal post-ischemic forearm blood flow (FBF) were investigated. Subjects with the CC genotype showed a significantly increased IMT (p<0.05) and a concommitantly reduced maximal FBF (p<0.01) as compared to those with the T allele. Thus, our results show that the polymorphism in the promoter region of OPG is associated with both vascular morphology and function in apparently healthy subjects.
authors.affiliation: Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Brändström
authors.forename: Fredrik
authors.initials: F
authors.lastname: Stiger
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Thomas
authors.initials: T
authors.lastname: Kahan
authors.forename: Håkan
authors.initials: H
authors.lastname: Melhus
authors.forename: Andreas
authors.initials: A
authors.lastname: Kindmark
mesh_terms: D000818:Animals; D001483:Base Sequence; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000502:physiology; D017931:DNA Primers; D005542:Forearm / Q000098:blood supply*; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D053244:Osteoprotegerin; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D012016:Reference Values; D012039:Regional Blood Flow; D013548:Sweden; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000502:physiology; D014463:Ultrasonography
chemical_list: D017931:DNA Primers; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse