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Genetic Variant HLA-DRB1*0403 and Therapeutic Response to Disease-Modifying Therapies in Multiple Sclerosis: A

Esteban Alejandro Gomez-Gaitan1, Yessica Eleanet Garcia-Ortega2, Ana Miriam Saldaña-Cruz3

  • 1Pharmacology Doctoral Program, Physiology Department, University Center for Health Sciences, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico.

International Journal of Molecular Sciences
|October 14, 2023
PubMed

Insights

This study found no association between the HLA-DRB1*0403 genetic variant and treatment response in Mexican patients with multiple sclerosis (MS) receiving disease-modifying therapies (DMTs). Further research is needed to identify genetic factors influencing DMT efficacy in MS.

Area of Science:

  • Neuroimmunology
  • Genetics
  • Pharmacogenomics

Background:

  • Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease causing neurodegeneration and disability.
  • A significant portion of MS patients (30-50%) exhibit suboptimal responses to disease-modifying therapies (DMTs).
  • Genetic factors, including specific variants, may influence individual therapeutic responses to DMTs in MS.

Purpose of the Study:

  • To investigate the association between the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in Mexican patients with MS.
  • To determine if the presence of HLA-DRB1*0403 impacts the achievement of No Evidence of Disease Activity (NEDA-3).

Main Methods:

  • A cohort of 105 Mexican patients diagnosed with MS was analyzed.
  • Therapeutic response was assessed using the NEDA-3 criteria (absence of clinical relapse, disability progression, and radiological activity).
  • HLA-DRB1*0403 genetic variant was genotyped using quantitative polymerase chain reaction (qPCR) with TaqMan probes.

Main Results:

  • The majority of MS patients (86.7%) achieved NEDA-3 while on DMTs.
  • Genotype frequencies for HLA-DRB1*0403 were GG (50.5%), GA (34.3%), and AA (15.2%).
  • No statistically significant difference in the frequency of the HLA-DRB1*0403 AA genotype was observed between patients achieving NEDA-3 (48.7%) and those who did not (43.1%, p=0.6).

Conclusions:

  • The HLA-DRB1*0403 genetic variant is not associated with therapeutic response to DMTs in the studied Mexican MS population.
  • These findings suggest that HLA-DRB1*0403 does not predict treatment efficacy in this cohort.
  • Further investigation into other genetic markers is warranted to understand DMT response variability in MS.
Keywords:
HLA-DRB1*0403multiple sclerosistherapeutic response

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