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Association of TNFAIP3 and TNFRSF1A variation with multiple sclerosis in a German case-control cohort.

Abstract

Variations in two genes of the tumour necrosis factor (TNF) alpha pathway have been implicated in the pathogenesis of autoimmune diseases: polymorphisms in the TNFRSF1A gene, encoding TNF receptor 1, showed significant association with MS in genomewide association scans, and variation in or near the TNFAIP3 gene, coding for a negative regulator of NFkB, was associated with MS, systemic lupus erythematosus, diabetes and rheumatoid arthritis. This study aimed at investigating association of MS with variation in the TNFRSF1A gene as well as in the TNFAIP3 gene region in an independent German case-control cohort. Four hundred and ninety-seven unrelated patients with MS and 878 healthy controls were genotyped with restriction enzyme digestion or TaqMan assays for three polymorphisms in the TNFRSF1A gene and seven in the region of the TNFAIP3 gene. Allele, genotype and haplotype frequencies were compared between cases and controls by chi-square testing. We found significant association of rs10499194, located in the intergenic region upstream of TNFAIP3, with MS (pc = 3.4 × 10(-4) ). Further, the intronic SNP rs1800693 in TNFRSF1A showed moderate association (pc = 0.033) with MS. In conclusion, evidence is accumulating that polymorphisms in both TNFAIP3 and TNFRSF1A genes play a role in MS pathogenesis. Additional studies are warranted to further elucidate the role of TNF pathway variation for MS development.

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  • Authors+Show Affiliations

    ,

    Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany.

    , , , ,

    Source

    MeSH

    Adult
    Alleles
    Case-Control Studies
    DNA-Binding Proteins
    Female
    Gene Frequency
    Genetic Association Studies
    Genetic Predisposition to Disease
    Genetic Variation
    Genotype
    Germany
    Haplotypes
    Humans
    Intracellular Signaling Peptides and Proteins
    Male
    Middle Aged
    Multiple Sclerosis
    Nuclear Proteins
    Odds Ratio
    Polymorphism, Single Nucleotide
    Receptors, Tumor Necrosis Factor, Type I
    Tumor Necrosis Factor alpha-Induced Protein 3

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    25684197

    Citation

    Hoffjan, S, et al. "Association of TNFAIP3 and TNFRSF1A Variation With Multiple Sclerosis in a German Case-control Cohort." International Journal of Immunogenetics, vol. 42, no. 2, 2015, pp. 106-10.
    Hoffjan S, Okur A, Epplen JT, et al. Association of TNFAIP3 and TNFRSF1A variation with multiple sclerosis in a German case-control cohort. Int J Immunogenet. 2015;42(2):106-10.
    Hoffjan, S., Okur, A., Epplen, J. T., Wieczorek, S., Chan, A., & Akkad, D. A. (2015). Association of TNFAIP3 and TNFRSF1A variation with multiple sclerosis in a German case-control cohort. International Journal of Immunogenetics, 42(2), pp. 106-10. doi:10.1111/iji.12183.
    Hoffjan S, et al. Association of TNFAIP3 and TNFRSF1A Variation With Multiple Sclerosis in a German Case-control Cohort. Int J Immunogenet. 2015;42(2):106-10. PubMed PMID: 25684197.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Association of TNFAIP3 and TNFRSF1A variation with multiple sclerosis in a German case-control cohort. AU - Hoffjan,S, AU - Okur,A, AU - Epplen,J T, AU - Wieczorek,S, AU - Chan,A, AU - Akkad,D A, Y1 - 2015/02/12/ PY - 2014/12/19/received PY - 2015/01/27/accepted PY - 2015/2/17/entrez PY - 2015/2/17/pubmed PY - 2015/12/15/medline SP - 106 EP - 10 JF - International journal of immunogenetics JO - Int. J. Immunogenet. VL - 42 IS - 2 N2 - Variations in two genes of the tumour necrosis factor (TNF) alpha pathway have been implicated in the pathogenesis of autoimmune diseases: polymorphisms in the TNFRSF1A gene, encoding TNF receptor 1, showed significant association with MS in genomewide association scans, and variation in or near the TNFAIP3 gene, coding for a negative regulator of NFkB, was associated with MS, systemic lupus erythematosus, diabetes and rheumatoid arthritis. This study aimed at investigating association of MS with variation in the TNFRSF1A gene as well as in the TNFAIP3 gene region in an independent German case-control cohort. Four hundred and ninety-seven unrelated patients with MS and 878 healthy controls were genotyped with restriction enzyme digestion or TaqMan assays for three polymorphisms in the TNFRSF1A gene and seven in the region of the TNFAIP3 gene. Allele, genotype and haplotype frequencies were compared between cases and controls by chi-square testing. We found significant association of rs10499194, located in the intergenic region upstream of TNFAIP3, with MS (pc = 3.4 × 10(-4) ). Further, the intronic SNP rs1800693 in TNFRSF1A showed moderate association (pc = 0.033) with MS. In conclusion, evidence is accumulating that polymorphisms in both TNFAIP3 and TNFRSF1A genes play a role in MS pathogenesis. Additional studies are warranted to further elucidate the role of TNF pathway variation for MS development. SN - 1744-313X UR - https://www.unboundmedicine.com/medline/citation/25684197/Association_of_TNFAIP3_and_TNFRSF1A_variation_with_multiple_sclerosis_in_a_German_case_control_cohort_ L2 - https://doi.org/10.1111/iji.12183 DB - PRIME DP - Unbound Medicine ER -