Associations of Vitamin D Receptor, Calcium-Sensing Receptor and Parathyroid Hormone Gene Polymorphisms with Calcium Homeostasis and Peripheral Bone Density in Adult Finns

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Abstract
Background: Thus far the search for osteoporosis candidate genes has focused less attention on the regulation of calcium homeostasis. Associations of vitamin D receptor (VDR) FokI, calcium-sensing receptor (CaSR) A986S and parathyroid hormone (PTH) BstBI polymorphisms with calcium homeostasis and peripheral bone density were investigated in adult Finns. Methods: The subgroup of the population-based FINRISK survey consists of 339 healthy adults aged 31–43 years. Lifestyle data were assessed with questionnaires and food diaries. DNA was isolated from blood, and biochemical determinants of calcium metabolism were measured from blood and 24-hour urine samples. Bone mineral density (BMD) was measured using the DXA method at the distal forearm and by quantitative ultrasound (broadband ultrasound attenuation and speed of sound) at the calcaneus. Subjects were genotyped for VDR FokI, CaSR A986S and PTH BstBI polymorphisms. Results: The CaSR 986S allele was associated with higher serum ionized calcium (p = 0.014). Forearm BMD was lowest for the PTH BstBI genotype bb in males (p = 0.023). VDR FokI and PTH BstBI polymorphisms showed a significant interaction on serum PTH (p = 0.010). The other gene–gene or diet–gene interactions studied showed no significant results. Conclusions: VDR, CaSR and PTH contribute to the genetic regulation of calcium homeostasis and peripheral bone density.