Pharmacogenomics Study for Raloxifene in Postmenopausal Female with Osteoporosis

Dis Markers. 2020 Aug 31:2020:8855423. doi: 10.1155/2020/8855423. eCollection 2020.

Abstract

Osteoporosis is characterized by decreased bone mineral density and increased risk of fracture. Raloxifene is one of the treatments of osteoporosis. However, the responses were variable among patients. Previous studies revealed that the genetic variants are involved in the regulation of treatment outcomes. To date, studies that evaluate the influence of genes across all genome on the raloxifene treatment response are still limited. In this study, a total of 41 postmenopausal osteoporosis patients under regular raloxifene treatment were included. Gene-based analysis using MAGMA was applied to investigate the genetic association with the bone mineral density response to raloxifene at the lumbar spine or femoral neck site. Results from gene-based analysis indicated several genes (GHRHR, ABHD8, and TMPRSS6) related to the responses of raloxifene. Besides, the pathways of iron ion homeostasis, osteoblast differentiation, and platelet morphogenesis were enriched which implies that these pathways might be relatively susceptible to raloxifene treatment outcome. Our study provided a novel insight into the response to raloxifene.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Bone Density Conservation Agents / therapeutic use*
  • Disease Models, Animal
  • Epoxide Hydrolases / genetics
  • Female
  • Genotyping Techniques
  • Humans
  • Membrane Proteins / genetics
  • Mice
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / genetics
  • Pharmacogenomic Variants*
  • Raloxifene Hydrochloride / therapeutic use*
  • Receptors, Neuropeptide / genetics
  • Receptors, Pituitary Hormone-Regulating Hormone / genetics
  • Serine Endopeptidases / genetics
  • Treatment Outcome

Substances

  • Bone Density Conservation Agents
  • GHRHR protein, human
  • Membrane Proteins
  • Receptors, Neuropeptide
  • Receptors, Pituitary Hormone-Regulating Hormone
  • Raloxifene Hydrochloride
  • Epoxide Hydrolases
  • Serine Endopeptidases
  • TMPRSS6 protein, human