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Interaction of HLA-DRB1*1501 allele and TNF-alpha -308 G/A single nucleotide polymorphism in the susceptibility to

Majid Shahbazi1, Danial Roshandel, Eskandar Omidnyia

  • 1Medical Cellular & Molecular Research Center, Talghani Children Hospital of Golestan, University of Medical Sciences, Bolv Janbazan, Gorgan, Iran. shahbazimajid@yahoo.co.uk

Clinical Immunology (Orlando, Fla.)
|March 15, 2011
PubMed

Insights

The HLA-DRB1*1501 allele and TNF-alpha -308 G/A polymorphism increase multiple sclerosis risk in Iranians. Their combined presence significantly elevates susceptibility, highlighting gene interactions in MS pathogenesis.

Area of Science:

  • Immunogenetics
  • Neuroimmunology

Background:

  • Multiple sclerosis (MS) is a complex, multifactorial neurological disorder.
  • Genetic factors, including Human Leukocyte Antigen (HLA) and cytokine genes, are implicated in MS pathogenesis.

Purpose of the Study:

  • To investigate the association of the HLA-DRB1*1501 allele and the TNF-alpha -308 G/A single nucleotide polymorphism (SNP) with MS susceptibility in the Iranian population.
  • To evaluate the potential interaction between these genetic markers in MS risk.

Main Methods:

  • Genomic DNA was extracted from 366 MS patients and 414 healthy controls.
  • Genotyping for HLA-DRB1*1501 and TNF-alpha -308 G/A polymorphism was performed using SSP-PCR.
  • Allele and genotype frequencies were compared using Fisher's exact test.

Main Results:

  • The HLA-DRB1*1501 allele was significantly more frequent in MS patients (OR=1.57, P=0.0026).
  • The TNF-alpha -308 G allele and G/G genotype were also associated with increased MS risk (G vs. A: OR=1.26, P<0.05; G/G vs. A/A: OR=4.59, P=0.0003).
  • A significant interaction was observed, with the co-existence of TNF G and HLA-DRB1*1501 alleles showing a higher prevalence in MS patients (OR=7.07, P=0.0007).

Conclusions:

  • Both HLA-DRB1*1501 and TNF-alpha -308 G/A polymorphism are risk factors for MS in the Iranian population.
  • Evidence supports a gene-gene interaction between HLA and cytokine genes in the development and pathogenesis of multiple sclerosis.

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