Osteoprotegerin Gene Polymorphisms in Men with Coronary Artery Disease

Abstract

Osteoprotegerin (OPG) antagonizes receptor activator of nuclear factor-kappaB ligand (RANKL), the principal regulator of osteoclasts. Of note, OPG-deficient mice display osteoporosis and arterial calcification. Recently, OPG gene polymorphisms have been associated with osteoporosis and early predictors of cardiovascular disease. In this study, we examined OPG gene polymorphisms in 468 men who had absence of coronary artery disease (CAD) or single-, double-, or triple-vessel disease on coronary angiography. Denaturing gradient gel electrophoresis followed by DNA sequencing revealed nucleotide substitutions 149 T-->C, 163 A-->G, 209 G-->A, 245 T-->G, 950 T-->C (all promoter), 1181 G-->C (exon 1), and 6890 A-->C (intron 4), respectively. Although single polymorphisms were not associated with CAD, linkage of polymorphisms 950 and 1181 revealed that haplotypes were overrepresented in men with CAD (chi(2) = 17.05; P = 0.03) with an increased risk of CAD in carriers of genotypes 950 TC/1181 GC and 950 CC/1181 CC (odds ratio, 1.67; 95% confidence interval, 1.02-2.72; P = 0.04). Furthermore, serum OPG levels were correlated with the presence of a C allele at position 950 (P = 0.02). In summary, linkage of genetic variations of the OPG gene at positions 950 and 1181 may confer an increased risk of CAD in Caucasian men.

The relation between the levels of osteoprotegerin and the degree of coronary artery disease in patients with acute coronary syndrome and stable angina pectoris

“…Another limitation is that we did not study the OPG vs. the RANKL polymorphism of the patients included in this study. The OPG polymorphism is known to be associated with cardiovascular disease [26,27]. Further, the OPG polymorphism carrier state may become a valuable molecular marker of the risk of CAD [28].…”

The relationship between Receptor Activator of Nuclear Factor-.KAPPA.B Ligand (RANKL) gene polymorphism and aortic calcification in Korean women

“…OPG gene polymorphisms with increased risk for coronary artery disease and osteoporotic fracture were reported [22][23][24][25], and recently, RANKL gene polymorphisms have been studied relative to bone mineral density and osteoporotic fracture [24,26,27]. However, there has been no reported data on the association of cardiovascular system with RANKL gene polymorphisms.…”

“…Gene polymorphisms in KLOTHO, which encodes a hormone with anti-aging properties that is involved in phosphate regulation, were reported to be associated with bone mineral density and coronary artery disease in Asian population [34][35][36]. Polymorphisms in OPG gene, which is a decoy receptor for RANKL, were reported to be associated with osteoporosis and increased risk of coronary artery disease and vascular morphology [22,37]. In a study performed in the same study population as this study, no significant relationship was found between four OPG gene polymorphisms and aortic calcification or cardiovascular risk factors [27].…”

TNFRSF11B (tumor necrosis factor receptor superfamily, member 11b)

“…Serum OPG levels have shown to have prognostic value in heart failure after acute myocardial infarction as well as in patients affected by abdominal aortic aneurysm and peripheral artery disease (Karan et al, 2005;Ziegler et al, 2005). Remarkably, two OPG genetic polymorphisms have been associated with an increased risk of coronary artery disease in Caucasian men, and serum OPG levels correlated with one of these polymorphisms (Soufi et al, 2004). Thus, these studies strongly indicate that serum OPG levels frequently rise in clinical conditions that favor vascular dysfunction or atherosclerosis.…”