Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women

Front Endocrinol (Lausanne). 2024 Apr 23:15:1392063. doi: 10.3389/fendo.2024.1392063. eCollection 2024.

Abstract

Introduction: Understanding the genetic factors contributing to variations in bone mineral density (BMD) and vitamin D could provide valuable insights into the pathogenesis of osteoporosis. This study aimed to evaluate the association of single nucleotide variants in MARK3 (rs11623869), PLCB4 (rs6086746), and GEMIN2 (rs2277458) with BMD in Mexican women.

Methods: The gene-gene interaction was evaluated in these variants in serum 25(OH)D levels and BMD. A genetic risk score (GRS) was created on the basis of the three genetic variants. Genotyping was performed using predesigned TaqMan assays.

Results: A significant association was found between the rs6086746-A variant and BMD at the total hip, femoral neck, and lumbar spine, in women aged 45 years or older. However, no association was observed between the variants rs11623869 and rs2277458. The rs11623869 × rs2277458 interaction was associated with total hip (p=0.002) and femoral neck BMD (p=0.013). Similarly, for vitamin D levels, we observed an interaction between the variants rs6086746 × rs2277458 (p=0.021). GRS revealed a significant association with total hip BMD (p trend=0.003) and femoral neck BMD (p trend=0.006), as well as increased vitamin D levels (p trend=0.0003). These findings provide evidence of the individual and joint effect of the MARK3, PLCB4, and GEMIN2 variants on BMD and serum vitamin D levels in Mexican women.

Discussion: This knowledge could help to elucidate the interaction mechanism between BMD-related genetic variants and 25OHD, contributing to the determination of the pathogenesis of osteoporosis and its potential implications during early interventions.

Keywords: bone mineral density; genetic association; genetic risk score; osteoporosis; postmenopausal; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bone Density* / genetics
  • Female
  • GTP-Binding Proteins / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Mexico
  • Middle Aged
  • Osteoporosis / blood
  • Osteoporosis / genetics
  • Polymorphism, Single Nucleotide*
  • Protein Serine-Threonine Kinases / genetics
  • Vitamin D* / analogs & derivatives
  • Vitamin D* / blood

Substances

  • Vitamin D
  • Protein Serine-Threonine Kinases
  • 25-hydroxyvitamin D
  • GTP-Binding Proteins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was partially funded by the Instituto Nacional de Medicina Genómica, grant number 266-17/2016/I and 399-07/2019/I. RV-C received funding from CONACYT under grant: INFR-2016-01-270405. RJ-O is supported by a Postdoctoral Fellowship from the Consejo Nacional de Ciencia y Tecnología (Grant Ciencia de Frontera CF 2019-102962). AB-C is the recipient of a Postdoctoral Fellowship from the Consejo Nacional de Humanidades, Ciencia y Tecnología (CONAHCYT-Estancia Posdoctoral de Incidencia Inicial 2022 with CVU 508876).