Interaction of HLA-DRB1* 1501 and TNF-Alpha in a Population-based Case-control Study of Multiple Sclerosis

Abstract

This study was conducted to determine whether single nucleotide polymorphisms (SNPs) in nine genes (human leukocyte antigen (HLA), T cell receptor beta (TCA receptor β), tumor necrosis factor α (TNF α), tumor necrosis factor β (TNF β), apolipoprotein E (APOE), interleukin 7 receptor alpha chain (IL7RA) interleukin 2 receptor alpha chain (IL2RA) myelin basic protein (MBP) and vitamin D receptor (VDR)) associated with multiple sclerosis (MS) could be replicated in a population-based sample, and to determine if these associations are modified by presence of HLA DRB1*1501. DNA was available from 722 individuals (223 with MS and 499 controls) who participated in a population-based case-control study. Cases and controls were matched on ancestry, age, gender and geographic area. HLA DRB1*1501 risk allele (T) was confirmed in this population using a genotypic test, controlling for multiple comparisons. Examining the effect of each SNP in the presence or absence of the HLA DRB1*1501 risk allele identified significant associations with TNF α -1031 (rs1799964) among those without the HLA risk allele. No additional interactions were significant in a cases-only analysis. Our results indicate that an interaction between SNPs in TNF α and HLA DRB1*1501 may influence the risk of developing MS.

Keywords: A-DRB1*1501; Case-Control Study; Genetic Susceptibility; Gene–Gene Interaction; Multiple Sclerosis; Tumor Necrosis Factor-Alpha.