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10.1371/journal.pone.0194693 http://scihub22266oqcxt.onion/10.1371/journal.pone.0194693 C5868803!5868803 !29579081     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29579081 &cmd=llinks): Failed to open stream: HTTP request failed! 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Genetics in TNF-TNFR pathway: A complex network causing spondyloarthritis and conditioning response to anti-TNF? therapy |pdf=|usr=}}{{29579081 }} gab.com Text Genetics in TNF-TNFR pathway: A complex network causing spondyloarthritis and conditioning response to anti-TNF therapy JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=29579081 #FOAvip OBJECTIVES: We investigated whether polymorphisms (SNPs) in the promoter region of TNFA, or in the autoinflammatory TNFRSF1A and MEFV genes, concur with HLA-B27 in enhancing the risk of Spondyloarthritis (SpA) and/or in predicting the response to anti-TNF? treatment. METHODS: 373 controls and 137 SpA (82 with Psoriatic Arthritis-PsA and 55 with Ankylosing Spondylitis- AS; 98/137 under TNF? inhibitor therapy) from the Veneto Region (Italy) were studied. TNFA polymorphisms (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) and HLA-B27 were assayed by RT-PCR. Direct sequencing of MEFV (exons 2,3,5 and 10) and TNFRSF1A (exons 2,3,4 and 6) genes were performed. RESULTS: HLA-B27 was associated with AS (?2 = 120.1; p = 0.000). Only the TNFA -1031T>C was singly associated with SpA, and the haplotype C/G, resulting from -1031T>C/-308G>A combination, was significantly associated with a reduced risk of SpA (OR: 0.67, CI: 0.46-0.97; p = 0.035). Two SNPs were identified in TNFRSF1A, the R92Q (Minor allele frequency-MAF = 0.034) and c.625+10A>G (MAF = 0.479). None of them was associated with SpA (p>0.05). The TNFRSF1A c.625+10 G allele was associated with late response to anti-TNF? therapy (p = 0.031). Twenty-one SNPs were identified in MEFV gene, 10 with a known potential functional significance. Variant alleles were extremely rare in our population (MAF<0.025) except for R202Q (MAF = 0.27). None was associated with SpA diagnosis (p>0.05). CONCLUSION: TNFRSF1A and MEFV gene SNPs are not associated with SpA in the North-East of Italy. AS risk appears to depend not only on HLA-B27, but also on the protective TNFA haplotype -1031C/-308G. The TNFRSF1A c.625+10A>G impacts on the response to anti-TNF? therapy. Twit Text FOAVip Genetics in TNF-TNFR pathway: A complex network causing spondyloarthritis and conditioning response to anti-TNF therapy ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=29579081 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29579081 #FOAvip English Wikipedia <ref>{{Cite pmid|29579081 }}</ref> Genetics in TNF-TNFR pathway: A complex network causing spondyloarthritis and conditioning response to anti-TNF? therapy #MMPMID29579081 Aita A ; Basso D ; Ramonda R ; Moz S ; Lorenzin M ; Navaglia F ; Zambon CF ; Padoan A ; Plebani M ; Punzi L PLoS One 2018[]; 13 (3 ): e0194693 PMID29579081 show ga OBJECTIVES: We investigated whether polymorphisms (SNPs) in the promoter region of TNFA, or in the autoinflammatory TNFRSF1A and MEFV genes, concur with HLA-B27 in enhancing the risk of Spondyloarthritis (SpA) and/or in predicting the response to anti-TNF? treatment. METHODS: 373 controls and 137 SpA (82 with Psoriatic Arthritis-PsA and 55 with Ankylosing Spondylitis- AS; 98/137 under TNF? inhibitor therapy) from the Veneto Region (Italy) were studied. TNFA polymorphisms (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) and HLA-B27 were assayed by RT-PCR. Direct sequencing of MEFV (exons 2,3,5 and 10) and TNFRSF1A (exons 2,3,4 and 6) genes were performed. RESULTS: HLA-B27 was associated with AS (?2 = 120.1; p = 0.000). Only the TNFA -1031T>C was singly associated with SpA, and the haplotype C/G, resulting from -1031T>C/-308G>A combination, was significantly associated with a reduced risk of SpA (OR: 0.67, CI: 0.46-0.97; p = 0.035). Two SNPs were identified in TNFRSF1A, the R92Q (Minor allele frequency-MAF = 0.034) and c.625+10A>G (MAF = 0.479). None of them was associated with SpA (p>0.05). The TNFRSF1A c.625+10 G allele was associated with late response to anti-TNF? therapy (p = 0.031). Twenty-one SNPs were identified in MEFV gene, 10 with a known potential functional significance. Variant alleles were extremely rare in our population (MAF<0.025) except for R202Q (MAF = 0.27). None was associated with SpA diagnosis (p>0.05). CONCLUSION: TNFRSF1A and MEFV gene SNPs are not associated with SpA in the North-East of Italy. AS risk appears to depend not only on HLA-B27, but also on the protective TNFA haplotype -1031C/-308G. The TNFRSF1A c.625+10A>G impacts on the response to anti-TNF? therapy. |Adult [MESH] |Alleles [MESH] |Antibodies, Monoclonal/*therapeutic use [MESH] |Arthritis, Psoriatic/drug therapy [MESH] |Biomarkers/analysis [MESH] |Female [MESH] |HLA-B27 Antigen/genetics/metabolism [MESH] |Haplotypes [MESH] |Humans [MESH] |Italy [MESH] |Logistic Models [MESH] |Male [MESH] |Middle Aged [MESH] |Odds Ratio [MESH] |Polymorphism, Single Nucleotide [MESH] |Promoter Regions, Genetic [MESH] |Pyrin/genetics [MESH] |Receptors, Tumor Necrosis Factor, Type I/genetics [MESH] |Spondylitis, Ankylosing/*drug therapy/genetics [MESH] |Tumor Necrosis Factor-alpha/*genetics/immunology [MESH]Genetics in TNF-TNFR pathway: A complex network causing spondyloarthri(epmc).pdf DeepDyve Pubget Overpricing