Associations of Serum Cathepsin K and Polymorphisms in CTSK Gene With Bone Mineral Density and Bone Metabolism Markers in Postmenopausal Chinese Women

Abstract

Cathepsin K plays an important role in bone resorption. The reports of the association of serum cathepsin K with bone mineral density (BMD) and bone turnover markers are conflicting and the role of serum cathepsin K as a bone turnover marker is unclear. The aims of the study were as follows: (1) to investigate the association of serum cathepsin K with BMD and markers of bone turnover and (2) to evaluate the correlations of single-nucleotide polymorphisms (SNPs) within the <i>CTSK</i> gene with serum cathepsin K, BMD, and markers of bone metabolism in postmenopausal Chinese women. A cross-sectional study was conducted with 1752 postmenopausal Chinese women. Four tagging SNPs (rs12085336, rs12746973, rs4379678, and rs10847) of the <i>CTSK</i> gene were genotyped. Serum cathepsin K of 768 and markers of bone metabolism of 1752 including serum intact PTH, 25-hydroxyvitamin D [25(OH)D], procollagen type 1 N-terminal propeptide (P1NP), and β-CrossLaps of type I collagen containing cross- linked C-telopeptide (β-CTX) were measured. The BMD of the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry (DXA). No significant relationship was detected between serum cathepsin K and age, BMI, BMD or bone metabolic markers (all <i>P</i> > 0.05) after adjustment for age and BMI. We failed to identify any significant association between the genotypes or haplotypes of <i>CTSK</i> and BMD, bone turnover markers, or serum cathepsin K. Neither serum cathepsin K nor <i>CTSK</i> gene polymorphisms was correlated with BMD or bone turnover markers. Genetic polymorphisms of <i>CTSK</i> may not be a major contributor to variations in the serum cathepsin K or BMD in postmenopausal Chinese women. The results implied that serum cathepsin K may not be viewed as a substitute for bone turnover markers.