Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification

Abstract

Osteoporosis is a major health problem affecting more than 75 million people throughout Europe, the United States, and Japan. Epidemiologic studies have determined that both genetic and environmental factors contribute to the pathogenesis of osteoporosis. We have investigated the association between polymorphisms at the osteocalcin locus and variables linked to bone health. Osteocalcin provides a link between bone and energy metabolism, hence its potential importance as an osteoporosis candidate gene. In this study, we included a total of 996 women (all aged 75 years) from the Osteoporosis Prospective Risk Assessment (OPRA) cohort. We sequenced the osteocalcin gene along with flanking regions to search for novel coding polymorphisms. We also analyzed four polymorphisms selected from within and flanking regions of the osteocalcin gene to study their association with serum total osteocalcin levels (STotalOC), total-body (TB) bone mineral density (BMD), fracture, TB fat mass, and body mass index (BMI). The promoter polymorphism rs1800247 was significantly associated with S-TotalOC ( p ¼ .012) after controlling for BMI and TB BMD. The polymorphism rs1543297 was significantly associated with prospectively occurring fractures ( p ¼ .008). In a model taking into account rs1543297 and rs1800247, along with TB BMD, BMI, smoking, and S-TotalOC, the polymorphisms together were able to identify an additional 6% of women who sustained a fracture ( p ¼ .02). We found no association between the polymorphisms and TB BMD, BMI, or TB fat mass. In conclusion, polymorphisms in and around the osteocalcin locus are significantly associated with S-TotalOC and fracture. Genotyping at the osteocalcin locus could add valuable information in the identification of women at risk of osteoporosis. ß

Associations of Serum Osteocalcin and Polymorphisms of<b> </b>the<b><i> Osteocalcin</i></b> Gene with Bone Mineral Density in Postmenopausal and Elderly Chinese Women

“…Deng et al [32] in 2002 reported that the h allele of the osteocalcin gene Hin dIII polymorphism was associated with higher hip BMD using traditional linkage or association approaches conducted in 630 Caucasians from 53 pedigrees. A study from Sweden included a total of 996 women, all aged 75 years, and revealed that the promoter polymorphism rs1800247 was significantly associated with serum total osteocalcin [22]. There are also studies that failed to demonstrate a correlation between rs1800247 and BMD.…”

“…Genetic variations in and around osteocalcin locus have been associated with serum osteocalcin concentrations and fracture in Caucasian women [22]. Many studies have revealed associations of the osteocalcin gene with BMD in various ethnic populations [23,24,25,26,27,28,29].…”

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

“…In this paper we analyse 'any incident fracture' which includes hip, distal radius, vertebra, shoulder, pelvis and proximal tibia. The majority of fractures recorded were attributable to low energy trauma [38]. Excluded were fractures of the face, hands and feet and fractures resulting from pathology and high energy trauma.…”

Increased trabecular bone and improved biomechanics in an osteocalcin null rat model created by CRISPR/Cas9 technology

“…Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap), is the most abundant noncollagenous protein in bone and comprises ∼1% of total body protein (McGuigan et al, 2010). An osteocalcin-deficient mouse model displays increased cortical bone thickness and density, trabecular bone and bone strength (Ducy et al, 1996).…”