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Updated: Jul 13, 2026
05:44
Modeling Multiple Sclerosis in the Two Sexes: MOG35-55-Induced Experimental Autoimmune Encephalomyelitis
Published on: October 13, 2023
IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis.
O H Kantarci1, A Goris, D D Hebrink
1Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Genes and Immunity
|January 28, 2005
Summary
Interferon-gamma (IFNgamma) gene variations influence multiple sclerosis (MS) risk differently in men and women. Specific IFNgamma gene polymorphisms increase MS susceptibility in males, suggesting a role in gender-based risk disparities.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- Multiple sclerosis (MS) affects women twice as often as men.
- Interferon-gamma (IFNgamma) treatment is known to be detrimental in MS.
- IFNgamma expression levels exhibit gender-specific variations.
Purpose of the Study:
- To investigate the association between genetic variations in the Interferon-gamma (IFNG) gene and multiple sclerosis (MS) susceptibility.
- To determine if these associations differ between genders.
- To explore the role of IFNG gene polymorphisms in the observed gender disparity in MS prevalence.
Main Methods:
- Studied population-based and hospital-based samples from the USA, Northern Ireland, and Belgium.
- Analyzed genetic variations including an intron 1 microsatellite [I1(761)*CAn] and a single nucleotide polymorphism [3'(325)*G --> A] near the IFNG gene.
- Stratified analyses by gender to assess differential susceptibility.
Main Results:
- Men carrying the 3'(325)*A allele of IFNG showed increased MS susceptibility in US and Northern Irish cohorts.
- A similar trend was observed in Belgian men, though not statistically significant.
- The I1(761)*CA13 allele, linked to 3'(325)*A, also increased MS susceptibility in men.
- Conversely, the I1(761)*CA12 allele was associated with decreased MS susceptibility in US men, consistent with findings in Sardinian men.
Conclusions:
- Genetic polymorphisms within the IFNG gene may contribute to the differing susceptibility to multiple sclerosis between men and women.
- Specific IFNG alleles appear to confer distinct risks for MS development in males.
- Further research is warranted to elucidate the precise mechanisms underlying gender-specific genetic influences on MS.
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