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F13A1 和 F13B 基因中的遗传倾向可预测腹部粘连形成:性别预后指标的鉴定。

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

机构信息

Department of Biomedical & Specialty Surgical Sciences and Centre Haemostasis & Thrombosis, Section of Medical Biochemistry, Molecular Biology & Genetics, University of Ferrara, corso Giovecca 203, 44121, Ferrara, Italy.

University Center for Studies on Gender Medicine, University of Ferrara, 44121, Ferrara, Italy.

出版信息

Sci Rep. 2018 Nov 16;8(1):16916. doi: 10.1038/s41598-018-35185-x.

Abstract

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.

摘要

腹部粘连(AA)是腹膜手术最常见的并发症,如果没有有效的预测生物标志物,肠梗阻是最严重的问题。抗 AA 屏障或粘连松解术并不能完全预防肠梗阻,尽管有证据表明它们可能减少相关并发症需要再次手术。此外,性别相关的倾向尚未得到充分研究。我们探索了凝血因子 XIII(F13A1 和 F13B 亚基基因)在接受剖腹手术的患者中的作用,这些患者大多采用中/下中线切口。总体而言,426 名患者(54%,♀)接受了 FXIIIA V34L(rs5985)、FXIIIA P564L(rs5982)、FXIIIA Y204F(rs3024477)和 FXIIIB H95R(rs6003)的 PCR-SNP 基因分型。患者的临床表型为:A 组(n=212),即发生 AA 的患者,其中 55.2%发生肠梗阻(亚组 A1),其余为亚组 A2;B 组(n=214)为未发生 AA(亚组 B1;53.3%)或症状/并发症(亚组 B2)的患者。不同的剖腹手术中,结肠手术与 AA 密切相关(OR=5.1;3.24-7.8;P<0.0001),不同性别评分(♀OR=5.33;2.32-12.23;P<0.0001 和♂OR=3.44;1.58-7.49;P<0.0001)。在 SNP 中,P564L(OR=4.42;1.45-13.4;P=0.008)和 Y204F(OR=7.78;1.62-37.3;P=0.01)显著预测肠梗阻,生存分析得出了有趣的性别差异(♀HR=5.28;2.36-11.8;P=0.00005;♂HR=2.22;1.31-3.85;P=0.0034)。预防 AA 的活性化合物属于抗凝/纤溶领域,表明它们是候选的研究目标。我们确定了新的预后标志物来预测 AA/肠梗阻,为设计新的治疗和性别预防方案提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292f/6240050/8d16b050ff22/41598_2018_35185_Fig1_HTML.jpg

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