Calcium sensing receptor gene polymorphism, circulating calcium concentrations and bone mineral density in healthy adolescent girls

Objective: Bone mineral density (BMD) in adolescence is under strong geneti c control, The calcium sensing receptor (CASR) is involved in the regulatio n of calcium homeostasis and bone resorption, The A986S polymorphism of the CASR has recently been associated with serum calcium levels, in one hither to unconfirmed report, We investigated whether this polymorphism was relate d to BMD, circulating calcium and parathyroid hormone (PTH) concentrations in girls. Design: BMD, plasma calcium and serum PTH were measured in adolescent girls and compared with regard to CASR genotype. Methods: In 97 healthy Caucasian girls (mean age 16.9 +/- 1.2 years (mean /- S.D.)), the A and S alleles were determined using PCR with a mismatched primer and the restriction enzyme BsaHI, BMD (g/cm(2)) of the total body, h umerus, femoral neck and lumbar spine was measured using dual energy X-ray absorptiometry. Results: The genotype frequencies were 71% AA, 26% AS and 3% SS, The genoty pes were divided into presence (29%) or absence of S allele (71%), Subjects with the S allele had higher levels of plasma calcium, corrected for album in (2.17 +/- 0.06 > 2.14 +/- 0.06; P < 0.05, using independent samples t-te st), lower BMD at the lumbar spine (P = 0.02) and total body (P = 0.04), an d were significantly less physically active (2.9 <plus/minus> 2.6 vs 4.3 +/ - 2.6 h/week; P = 0.01) than the subjects lacking the S allele, PTH levels were not significantly different between the two allelic groups, A multiple regression analysis, including age, height, weight and physical activity, revealed that the CASR allelic variants were not independent predictors of BMD at any site measured (beta = -0.03-0.09; P > 0.05). Physical activity w as an independent predictor of BMD, was significantly different between the CASR genotypes, and could therefore have a role in explaining the differen ce in BMD between the CASR genotypes. Conclusions: The CASR alleles are related to BMD, but it cannot be definite ly concluded whether the CASR polymorphism has a direct influence on BMD, o r whether the differences in BMD were mediated via an influence of the amou nt of physical activity.