Interaction ofHLA-DRB1*1501andTNF-Alphain a Population-based Case-control Study of Multiple Sclerosis.
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 ofHLA 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*1501risk 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 theHLA DRB1*1501risk allele identified significant associations withTNF 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.
Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, 30333, United States.
Dhelia M
DM
Williamson
Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3A 1R9.
Ruth Ann
RA
Marrie
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, 27710, United States.
Allison
A
Ashley-Koch
Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, 30333, United States.
Glen A
GA
Satten
A-DRB1*1501; Case-Control Study; Genetic Susceptibility; Gene–Gene Interaction; Multiple Sclerosis; Tumor Necrosis Factor-Alpha