Relationship between VKORC1 single nucleotide polymorphism 1173C>T, bone mineral density & carotid intima-media thickness

BACKGROUND & OBJECTIVES: The effects of vitamin K-dependent proteins in bone mineralization and vascular calcification and the implication of vitamin K epoxide reductase gene (VKORC1) 1173C>T polymorphism in warfarin sensitivity are well known. The main objective of the study was to investigate the relationship between VKORC1 1173C>T polymorphism, bone mineral density (BMD), and atherosclerosis (evaluated by intima-media thickness of the carotid artery and the presence of calcified plaques) in patients suspected to have osteoporosis or osteopenia and referred for BMD determination. METHODS: VKORC1 1173C>T polymorphism was evaluated in 239 consecutive patients referred by their physicians for BMD measurement (dual energy X-ray absorptiometry at L2-L4 lumbar spine, femoral neck and total hip). Ultrasonography of the carotid arteries was performed, intima-media thickness (IMT) was measured and the presence of atherosclerotic calcified plaques was recorded. RESULTS: In the patients with osteoporosis and osteopenia there was a higher frequency of TT genotype of VKORC1 1173C>T (P=0.04). The TT genotype was significantly more frequent in the osteoporotic group compared to the osteopenic group (P=0.01). The mean age and body mass index were lower in the patients with normal BMD and TT genotype (P=0.02, P=0.03). There was no correlation between the IMT and VKORC1 1173C>T genotype but the TT genotype had a significant association with the presence of calcified atherosclerotic plaques (P=0.05). This finding was not correlated with normal or pathologic BMD. INTERPRETATION & CONCLUSIONS: VKORC1 1173C>T polymorphism (TT genotype) was associated with osteoporosis and calcified plaques in the carotid artery in patients referred for BMD measurement. Different mechanisms are probably involved in these associations. TT genotype may serve as a potential genetic marker for the risk of OP and ATS.