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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.

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