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DRB1 Val86/Val86 Genotype
Associates With Multiple Sclerosis In Australia


Teutsch SM, Bennetts BH, Buhler MM, Heard RN, Stewart GJ
Hum Immunol 1999 Aug;60(8):715-22
Westmead Hospital, Dept of Clinical Immunology, NSW, Australia
PMID# 10439317; UI# 99368172
Abstract

Genetic susceptibility to Multiple Sclerosis (MS) has so far been strongly localized to the MHC Class II region encoding the alleles of the haplotype HLA-DRB1*1501, -DQA1*0102, -DQB1*0602.

However, this haplotype is not carried by approximately 40% of MS patients; a potential explanation could be that they carry other MHC Class II alleles with similar function due to the sharing of nucleotide sequences encoding critical Amino Acid residues. The DRB1 Gene is polymorphic at residue 86, encoding Valine or Glycine.

In view of the increasing evidence for a functional role for DRB1 aa86 in the binding and presentation of AutoAntigenic peptides such as Myelin Basic Protein, this study investigated associations with the residue 86 polymorphism in an Australian MS population.

A significant increase in the Val86/Val86 genotype was observed in the MS patients, which was still present in the absence of the DRB1*1501 allele (p = 0.032). This suggest that DRB1 aa86 may have an independent role in contributing to MS susceptibility.

The Val86/Val86 genotype was correlated with genotyping for other putative MS susceptibility Genes, including T-Cell receptor beta chain germline polymorphisms, HLA-DMB alleles, and -DQA1 and -DQB1 alleles encoding critical Amino Acid residues, with a significant interaction only observed with DQB1 Leu26 (p = 0.014).

Additional studies of the HLA-DRB1 aa86 polymorphism in MS, and its function, are needed to more fully understand this association.



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