PTHR1 Genetic Polymorphisms Are Associated with Osteoporosis among Postmenopausal Arab Women

Abstract

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1–L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO ( $\text{OR}=1.49$ , 95% CI 1.0-2.1, $P=0.03$ ). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; $P=0.048$ ]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.