Osteocalcin: Genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis

Osteocalcin is an abundant, highly conserved bone-specific protein that is synthesized by osteoblasts. Temporally, osteocalcin appears in embryonic bo ne at the time of mineral deposition, where it binds to hydroxyapatite in a calcium-dependent manner. A role for osteocalcin in bone resorption has be en suggested because of its ability to influence recruitment and differenti ation of osteoclasts at the bone surface. The human osteocalcin gene has be en mapped to 1q25-1q31 by somatic cell hybridization. In this paper, we ref ine both the genetic map and the physical map of osteocalcin and describe a new microsatellite (CA) marker, D1S3737, which is tightly linked to the ge ne. This marker and two other closely linked markers were used to identify alleles of the osteocalcin gene in case and control samples of postmenopaus al white Iowans with low and high bone mineral density (BMD), respectively. A significant difference (P = 0.007) was observed between allele frequency distributions of case and control women with one of the markers, D1S3737. Further, logistic regression analysis determined one allele of D1S3737 as a ssociated with BMD status in this population (P = 0.03). Our data suggest t hat genetic variation at the osteocalcin locus impacts BMD levels in the po stmenopausal period and may predispose some women to osteoporosis. (C) 1999 Academic Press.