37 research outputs found

    Genetics in TNF-TNFR pathway: A complex network causing spondyloarthritis and conditioning response to anti-TNFα therapy

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    <div><p>Objectives</p><p>We investigated whether polymorphisms (SNPs) in the promoter region of <i>TNFA</i>, or in the autoinflammatory <i>TNFRSF1A</i> and <i>MEFV</i> genes, concur with <i>HLA-B27</i> in enhancing the risk of Spondyloarthritis (SpA) and/or in predicting the response to anti-TNFα treatment.</p><p>Methods</p><p>373 controls and 137 SpA (82 with Psoriatic Arthritis-PsA and 55 with Ankylosing Spondylitis- AS; 98/137 under TNFα inhibitor therapy) from the Veneto Region (Italy) were studied. <i>TNFA</i> polymorphisms (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) and <i>HLA-B27</i> were assayed by RT-PCR. Direct sequencing of <i>MEFV</i> (exons 2,3,5 and 10) and <i>TNFRSF1A</i> (exons 2,3,4 and 6) genes were performed.</p><p>Results</p><p><i>HLA-B27</i> was associated with AS (χ<sup>2</sup> = 120.1; p = 0.000). Only the <i>TNFA</i> -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 <i>TNFRSF1A</i>, 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 <i>TNFRSF1A</i> c.625+10 G allele was associated with late response to anti-TNFα therapy (p = 0.031). Twenty-one SNPs were identified in <i>MEFV</i> 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).</p><p>Conclusion</p><p><i>TNFRSF1A</i> and <i>MEFV</i> gene SNPs are not associated with SpA in the North-East of Italy. AS risk appears to depend not only on <i>HLA-B27</i>, but also on the protective <i>TNFA</i> haplotype -1031C/-308G. The <i>TNFRSF1A</i> c.625+10A>G impacts on the response to anti-TNFα therapy.</p></div

    MOESM5 of MALDI-TOF peptidomic analysis of serum and post-prostatic massage urine specimens to identify prostate cancer biomarkers

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    Additional file 5: Results. Monte Carlo simulations results confirmed that substituting the limit of detection (LOD) with LOD/2 does not affect the reliability of ICC estimation; The measurement error structure of peptidomi MALDI-TOF/MS-based analysis of the urinary and serum feature

    Demographic, clinical characteristics, laboratory indices and outcome measures.

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    <p><b>The demographic characteristics were those obtained at enrolment, while patients’ clinical data and laboratory indices are referred to findings obtained at diagnosis of AS or PsA disease</b>.</p
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