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Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicators

Abdominal adhesions (AA) account for the most common complication of peritoneal surgery with bowel obstruction being the severest problem in the absence of effective predicting biomarkers. Anti-AA-barriers or adhesiolysis did not completely prevent bowel obstruction, although there is evidence they...

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Autores principales: Gemmati, Donato, Occhionorelli, Savino, Tisato, Veronica, Vigliano, Marco, Longo, Giovanna, Gonelli, Arianna, Sibilla, Maria G., Serino, Maria L., Zamboni, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240050/
https://www.ncbi.nlm.nih.gov/pubmed/30446716
http://dx.doi.org/10.1038/s41598-018-35185-x
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author Gemmati, Donato
Occhionorelli, Savino
Tisato, Veronica
Vigliano, Marco
Longo, Giovanna
Gonelli, Arianna
Sibilla, Maria G.
Serino, Maria L.
Zamboni, Paolo
author_facet Gemmati, Donato
Occhionorelli, Savino
Tisato, Veronica
Vigliano, Marco
Longo, Giovanna
Gonelli, Arianna
Sibilla, Maria G.
Serino, Maria L.
Zamboni, Paolo
author_sort Gemmati, Donato
collection PubMed
description Abdominal adhesions (AA) account for the most common complication of peritoneal surgery with bowel obstruction being the severest problem in the absence of effective predicting biomarkers. Anti-AA-barriers or adhesiolysis did not completely prevent bowel obstruction, although there is evidence they might reduce related complications requiring reoperation. In addition, gender-related predispositions have not been adequately investigated. We explored the role of coagulation Factor XIII (F13A1 and F13B subunit-genes) in patients following laparotomy, mostly median/lower median incision line. Globally, 426 patients (54%,♀), were PCR-SNP-genotyped for FXIIIA V34L (rs5985), FXIIIA P564L (rs5982), FXIIIA Y204F (rs3024477) and FXIIIB H95R (rs6003). Patients’ clinical phenotypes were: Group-A (n = 212), those who developed AA, and 55.2% of them developed bowel obstruction (subgroup-A1), the remaining were subgroup-A2; Group B (n = 214) were those who did not develop AA (subgroup-B1; 53.3%) or symptoms/complications (subgroup-B2). Among different laparotomy, colon surgery associated with AA at a major extent (OR = 5.1; 3.24–7.8; P < 0.0001) with different gender scores (♀OR = 5.33; 2.32–12.23; P < 0.0001 and ♂OR = 3.44; 1.58–7.49; P < 0.0001). Among SNPs, P564L (OR = 4.42; 1.45–13.4; P = 0.008) and Y204F (OR = 7.78; 1.62–37.3; P = 0.01) significantly predicted bowel obstruction and survival-analyses yielded interesting gender distinctions (♀HR = 5.28; 2.36–11.8; P = 0.00005; ♂HR = 2.22; 1.31–3.85; P = 0.0034). Active compounds preventing AA belong to the anticoagulant/fibrinolysis areas, suggesting them candidate investigation targets. We identified novel prognostic markers to predict AA/bowel obstruction giving insights to design novel therapeutic and gender prevention programs.
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spelling pubmed-62400502018-11-23 Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicators Gemmati, Donato Occhionorelli, Savino Tisato, Veronica Vigliano, Marco Longo, Giovanna Gonelli, Arianna Sibilla, Maria G. Serino, Maria L. Zamboni, Paolo Sci Rep Article Abdominal adhesions (AA) account for the most common complication of peritoneal surgery with bowel obstruction being the severest problem in the absence of effective predicting biomarkers. Anti-AA-barriers or adhesiolysis did not completely prevent bowel obstruction, although there is evidence they might reduce related complications requiring reoperation. In addition, gender-related predispositions have not been adequately investigated. We explored the role of coagulation Factor XIII (F13A1 and F13B subunit-genes) in patients following laparotomy, mostly median/lower median incision line. Globally, 426 patients (54%,♀), were PCR-SNP-genotyped for FXIIIA V34L (rs5985), FXIIIA P564L (rs5982), FXIIIA Y204F (rs3024477) and FXIIIB H95R (rs6003). Patients’ clinical phenotypes were: Group-A (n = 212), those who developed AA, and 55.2% of them developed bowel obstruction (subgroup-A1), the remaining were subgroup-A2; Group B (n = 214) were those who did not develop AA (subgroup-B1; 53.3%) or symptoms/complications (subgroup-B2). Among different laparotomy, colon surgery associated with AA at a major extent (OR = 5.1; 3.24–7.8; P < 0.0001) with different gender scores (♀OR = 5.33; 2.32–12.23; P < 0.0001 and ♂OR = 3.44; 1.58–7.49; P < 0.0001). Among SNPs, P564L (OR = 4.42; 1.45–13.4; P = 0.008) and Y204F (OR = 7.78; 1.62–37.3; P = 0.01) significantly predicted bowel obstruction and survival-analyses yielded interesting gender distinctions (♀HR = 5.28; 2.36–11.8; P = 0.00005; ♂HR = 2.22; 1.31–3.85; P = 0.0034). Active compounds preventing AA belong to the anticoagulant/fibrinolysis areas, suggesting them candidate investigation targets. We identified novel prognostic markers to predict AA/bowel obstruction giving insights to design novel therapeutic and gender prevention programs. Nature Publishing Group UK 2018-11-16 /pmc/articles/PMC6240050/ /pubmed/30446716 http://dx.doi.org/10.1038/s41598-018-35185-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Gemmati, Donato
Occhionorelli, Savino
Tisato, Veronica
Vigliano, Marco
Longo, Giovanna
Gonelli, Arianna
Sibilla, Maria G.
Serino, Maria L.
Zamboni, Paolo
Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicators
title Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicators
title_full Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicators
title_fullStr Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicators
title_full_unstemmed Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicators
title_short Inherited genetic predispositions in F13A1 and F13B genes predict abdominal adhesion formation: identification of gender prognostic indicators
title_sort inherited genetic predispositions in f13a1 and f13b genes predict abdominal adhesion formation: identification of gender prognostic indicators
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240050/
https://www.ncbi.nlm.nih.gov/pubmed/30446716
http://dx.doi.org/10.1038/s41598-018-35185-x
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