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.

Nyckelord

Animals

Base Sequence

Carotid Artery; Common/physiology/ultrasonography

DNA Primers

Forearm/*blood supply

Glycoproteins/deficiency/*genetics

Humans

Mice

Mice; Knockout

Muscle; Smooth; Vascular/*physiology

Osteoprotegerin

Polymerase Chain Reaction

Polymorphism; Genetic

Polymorphism; Single Nucleotide

Promoter Regions (Genetics)

Receptors; Cytoplasmic and Nuclear/deficiency/*genetics

Receptors; Tumor Necrosis Factor/antagonists & inhibitors

Reference Values

Regional Blood Flow

Sweden

Tunica Intima/physiology/ultrasonography

MEDICINE

MEDICIN

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)