A single nucleotide polymorphism in the promoter region of the human gene for osteoprotegerin is related to vascular morphology and function.
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.
Brändström
Helena
H
Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
Stiger
Fredrik
F
Lind
Lars
L
Kahan
Thomas
T
Melhus
Håkan
H
Kindmark
Andreas
A
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
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