Effects of the CASR rs104893706 gain-of-function mutation on bone mineral density in postmenopausal women by advanced age and smoking

Background and Aims: The G protein-coupled calcium-sensing receptor (CaSR) plays an important role in extracellular calcium homeostasis and regulation of parathyroid hormone (PTH) secretion. There are more than 300 activating/inactivating mutations in the CASR gene. However, the effects of both CaSR protein and CASR gene on bone mineral density (BMD) have not been investigated enough. The aim of this study was therefore to determine the effect of rs104893706 (A843E, (Ala to Glu at codon843)), a gain-of-function mutation of the CASR gene, on BMD in postmenopausal women. Methods: We studied the CASR A843E variation using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism methods in 180 postmenopausal women. Statistical analyses were performed using SPSS software package (version 21.0 SPSS Inc., Chicago, IL, U.S.A.). Results: No minor A allele, homozygous (AA) or heterozygous (CA), was observed in the study population. In other words, the frequency of the CASR A843E common CC genotype was 100%. BMD levels of the lumbar spine (L1-L4), femoral neck, and total hip were 1.03 [+ or -] 0.13g/[cm.sup.2], 0.87 [+ or -] 0.11g/[cm.sup.2], and 0.93 [+ or -] 0.11g/[cm.sup.2], respectively. Although the femoral neck (p=0.017), upper neck (p=0.040), lower neck (p=0.011), and Ward's triangle BMD values (p=0.005) were found significantly higher in younger postmenopausal women (age=55 years), there were no significant differences on BMD value of the lumbar spines, trochanter, and total hip between the age groups (p>0.05). Conclusion: Our findings confirm the effects of advanced age in favor of decreased BMD in postmenopausal women. This study suggests that the CASR A843E gain-of-function mutation may not be associated with bone mineral density and osteoporosis risk since we did not detect the A843E variation in Turkish postmenopausal women. Keywords: Osteoporosis, Calcium-sensing receptor, Gain-of-function mutation, Bone mineral density, Smoking