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Association of TNFAIP 3 and TNFRSF 1 A variation with multiple sclerosis in a German case–control cohort
Author(s) -
Hoffjan S.,
Okur A.,
Epplen J. T.,
Wieczorek S.,
Chan A.,
Akkad D. A.
Publication year - 2015
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/iji.12183
Subject(s) - pathogenesis , haplotype , biology , allele , gene , genetics , snp , single nucleotide polymorphism , immunology , genotype , medicine
Summary Variations in two genes of the tumour necrosis factor ( TNF ) alpha pathway have been implicated in the pathogenesis of autoimmune diseases: polymorphisms in the TNFRSF 1A gene, encoding TNF receptor 1, showed significant association with MS in genomewide association scans, and variation in or near the TNFAIP 3 gene, coding for a negative regulator of NF kB, was associated with MS , systemic lupus erythematosus, diabetes and rheumatoid arthritis. This study aimed at investigating association of MS with variation in the TNFRSF 1A gene as well as in the TNFAIP 3 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 TNFRSF 1A gene and seven in the region of the TNFAIP 3 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 TNFAIP 3, with MS ( p c = 3.4 × 10 −4 ). Further, the intronic SNP rs1800693 in TNFRSF 1A showed moderate association ( p c = 0.033) with MS . In conclusion, evidence is accumulating that polymorphisms in both TNFAIP 3 and TNFRSF 1A genes play a role in MS pathogenesis. Additional studies are warranted to further elucidate the role of TNF pathway variation for MS development.