Investigation of ACE rs4646994, MTHFR rs1801133 and VDR rs2228570 Genotypes in Jordanian Patients with Fibromyalgia Syndrome

Endocr Metab Immune Disord Drug Targets. 2021;21(10):1920-1928. doi: 10.2174/1871530321666201223104622.


Background: Fibromyalgia syndrome (FMS) is a chronic disease characterized by widespread body pain, weakness in certain parts of the body (critical points), low pain tolerance, sleep disturbances, and fatigue. This syndrome is considered rare in Jordan.

Objectives: The research aimed to find out the association of the angiotensin converting enzyme, methylenetetrahydrofolate reductase, and vitamin D receptor (ACE, MHFTR, and VDR, respectively) genotypes with FMS among Jordanian patients.

Methods: This work included 22 FM patients and 22 healthy individuals of Jordanian Arabic origin. The ACE rs4646994, MTHFR rs1801133, and VDR rs2228570 genotypes were determined using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism.

Results: No associations between ACE rs4646994, MTHFR rs1801133, and VDR rs2228570 with the vulnerability of a person for the development of FMS were found. However, we found an association between the ACE rs4646994 genotype and restless leg among FM patients.

Conclusion: Based on the result from this study, it appears that the ACE rs4646994 genotype is associated with restless leg among FMS patients of Jordanian origin. Further clinical investigations with larger sample sizes are required to confirm these findings and understand the molecular mechanism of ACE rs4646994 genetic variant in the restless leg syndrome among FM patients.

Keywords: ACE rs4646994; Jordan; Jordanian patients.; MTHFR rs1801133; VDR rs2228570; fibromyalgia syndrome.

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Fibromyalgia / epidemiology
  • Fibromyalgia / genetics*
  • Fibromyalgia / pathology
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Jordan / epidemiology
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Receptors, Calcitriol / genetics*
  • Risk Factors
  • Syndrome


  • Receptors, Calcitriol
  • VDR protein, human
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • ACE protein, human
  • Peptidyl-Dipeptidase A