Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: A systematic review and meta-analysis

BACKGROUND: Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis, crucial for normal functioning of the kidneys, bones, heart, and nervous system. Different pathologic conditions can affect serum PTH level resulting in hyperparathyroidism or hypoparathyroidism. Our study assessed the association of previously reported polymorphisms with the level of PTH (expressed in pg/mL) among individuals with different pathologic conditions affecting PTH level. METHODS: We searched Web of Science, MEDLINE, and Scopus to identify relevant articles published up to July 2017. The search yielded 6967 publications of which 44 fulfilled the inclusion criteria. We conducted meta-analyses for calcium-sensing receptor gene (CaSR) rs1801725 polymorphism in patients with primary hyperparathyroidism and vitamin D receptor gene (VDR) rs1544410 polymorphism in patients with end-stage renal disease (ESRD). RESULTS: None of the polymorphisms were significantly associated with PTH levels in the overall population. In subgroup analysis by ethnicity for VDR rs1544410 gene polymorphism, we found significant differences under dominant model (SMD: −0.18 [−0.32, −0.05], P < .01) and AA versus GG comparison (SMD: −0.29 [−0.52, −0.06], P < .01) in Asian patients with ESRD, while nominally significant results (P < .05) were observed for AG versus GG and AA versus GG comparisons in European individuals with ESRD. CONCLUSION: Scientific evidence of genetic association of serum PTH level among individuals with different pathologic conditions remains deficient and published results provide weak evidence. Further well-conducted studies on larger sample sets designed according to evidence-based principles are warranted to assure clinically applicable findings.