A Single-Nucleotide Polymorphism in the Gene Encoding Osteoprotegerin Is Associated With Diastolic Blood Pressure in Older Men

BACKGROUND: Osteoprotegerin (OPG) has been associated with cardiovascular events but currently the mechanisms underlying this association are unknown. OPG is thought to play a role in controlling artery calcification and small studies have suggested that it may influence artery structure. We examined the association between single nucleotide polymorphisms (SNPs) in the gene encoding OPG (tumor necrosis factor receptor superfamily, member 11b, TNFRSF11B), with blood pressure in a large cohort of elderly men. METHODS: 21 tagging SNPs in the region encoded by TNFRSF11B were examined in 1,071 men recruited in a population-based study of elderly men. Genotyping was carried out using the Illumina Golden Gate assay. SNPs were investigated for their association with resting systolic and diastolic blood pressure after adjusting for other variables using linear regression. The association of SNPs in the region encoded by TNFRSF11B with plasma OPG was assessed in a random subset of 467 men. RESULTS: One SNP, rs11573901, was significantly associated with diastolic blood pressure, after adjusting for other risk factors and multiple testing (coefficient -4.36, P = 0.001). Men with the TC genotype had lower diastolic blood pressure than those with the common cc variation. this snp was not associated with plasma opg in the 467 men in which this was examined. CONCLUSIONS: This study suggests that a SNP within the region encoded by TNFRSF11B, which is believed to code for OPG, is associated with blood pressure. The mechanism underlying this observed association is currently unclear.