HLA class II polymorphism in Latin American patients with multiple sclerosis

Autoimmun Rev. 2010 Apr;9(6):407-13. doi: 10.1016/j.autrev.2009.11.001. Epub 2009 Nov 5.

Abstract

Objective: To identify HLA-DRB1 alleles contributing to susceptibility to multiple sclerosis (MS) in a Colombian population and to estimate the common effect size of HLA class II on MS susceptibility in Latin American populations through a meta-analysis.

Methods: A total of 65 Colombian patients with MS and 184 matched controls were included. HLA-DRB1 typing was done using the sequence-specific oligonucleotide probe method. A bivariate and a multivariate logistic regression analyses were done. Case-control studies performed in Latin America were searched up to January 2009 through a systematic review of the literature. Effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by means of the random effect model.

Results: A total of 464 cases and 2581 controls from 7 studies and the results of the present study in Colombians were analyzed. HLA-DRB1*15 (OR: 2.3; 95% CI: 1.68-3.07; p<0.001) and HLA-DQB1*06 (OR: 2.2; 95% CI: 1.54-3.07; p<0.001) groups as well as DRB1*1501 (OR: 2.6; 95% CI: 1.67-4.02; p<0.001), DRB1*1503 (OR: 2.2; 95% CI: 1.39-3.62; p=0.001) and DQB1*0602 (OR: 2.5; 95% CI: 1.66-3.71; p<0.001) alleles were found to be risk factors for MS. The myelin basic protein immunodominant sequence (221)VHFFKNIVT(229) was predicted to strongly and simultaneously bind to HLA-DRB1*1501 and *1503.

Conclusion: The current study highlights the effect size of HLA class II in MS in Latin America and confirms similar allelic risk factors across diverse populations. Receptor-ligand interactions in the HLA-antigenic peptide complex could have potential predictive and therapeutical implications.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Autoantigens / metabolism
  • Case-Control Studies
  • Colombia
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • HLA-DQ Antigens / genetics*
  • HLA-DQ Antigens / metabolism
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / metabolism
  • HLA-DRB1 Chains
  • Histocompatibility Testing
  • Humans
  • Male
  • Multiple Sclerosis / epidemiology*
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology*
  • Myelin Basic Protein / metabolism
  • Peptide Fragments / metabolism
  • Polymorphism, Genetic
  • Protein Binding
  • Risk Factors

Substances

  • Autoantigens
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Myelin Basic Protein
  • Peptide Fragments