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AJG:与蛋白酶敏感的胰脂肪酶基因变体与慢性胰腺炎早期发作相关

2019-06-19 不详 MedSci原创

胰腺内的蛋白消化酶胰蛋白酶的过早激活是胰腺炎发病机制中的关键因素。影响胰腺内胰蛋白酶活性基因的突变与慢性胰腺炎(CP)有关。最近,羧基酯脂肪酶作为胰蛋白酶非依赖性风险基因被证明与胰腺炎的发作有关,因此,本项研究旨在评估胰脂肪酶(PNLIP)作为CP的潜在新型易感基因的可能性。

背景及目标:
胰腺内的蛋白消化酶胰蛋白酶的过早激活是胰腺炎发病机制中的关键因素。影响胰腺内胰蛋白酶活性基因的突变与慢性胰腺炎(CP)有关。最近,羧基酯脂肪酶作为胰蛋白酶非依赖性风险基因被证明与胰腺炎的发作有关,因此,本项研究旨在评估胰脂肪酶(PNLIP)作为CP的潜在新型易感基因的可能性。

方法:
研究人员分析了德国429名非酒精性CP患者和600名对照受试者以及法国632名非酒精性CP患者和957名对照患者,以及来自日本的223名非酒精性CP患者和1070名对照患者的所有13个PNLIP外显子基因,此外,研究人员还评估了重组PNLIP变体的细胞分泌,脂肪酶活性和蛋白水解稳定性。

结果:
在德国人群队列中,研究人员发现8/429(1.9%)患者和2/600(0.3%)对照携带PNLIP错义变异(P = 0.02,优势比[OR] = 5.7,95%置信区间[CI] = 1.1-38.9)。在患者中检测到的变体易于通过胰蛋白酶和胰凝乳蛋白酶进行蛋白水解降解。在法国人群队列中,蛋白酶敏感变异体也富含早发性CP患者(5/632 [0.8%]),而不是在对照组中(1/957 [0.1%])(P = 0.04,OR = 7.6,95)95%CI = 0.9-172.9)。相反,在非欧洲人群中未检测到蛋白酶敏感变体。

结论:
本项研究结果表明蛋白酶敏感的PNLIP变异是CP发病的遗传风险因素。

原始出处:
Lasher, Denise. Et al. Protease-Sensitive Pancreatic Lipase Variants Are Associated With Early Onset Chronic Pancreatitis. American Journal of Gastroenterology. 2019.

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    2020-04-04 canlab
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    2019-07-12 tidiq
  3. [GetPortalCommentsPageByObjectIdResponse(id=1945208, encodeId=ff311945208d9, content=<a href='/topic/show?id=249488e60fe' target=_blank style='color:#2F92EE;'>#蛋白酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88760, encryptionId=249488e60fe, topicName=蛋白酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=512d422, createdName=canlab, createdTime=Sat Apr 04 22:29:00 CST 2020, time=2020-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1672109, encodeId=df6c16e210966, content=<a href='/topic/show?id=860584396ef' target=_blank style='color:#2F92EE;'>#脂肪酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84396, encryptionId=860584396ef, topicName=脂肪酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1fae26881555, createdName=tidiq, createdTime=Fri Jul 12 20:29:00 CST 2019, time=2019-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2057267, encodeId=44b1205e2676f, content=<a href='/topic/show?id=18982222db' target=_blank style='color:#2F92EE;'>#AJG#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2222, encryptionId=18982222db, topicName=AJG)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2978132, createdName=minzju5052, createdTime=Tue Feb 18 17:29:00 CST 2020, time=2020-02-18, status=1, ipAttribution=)]
    2020-02-18 minzju5052
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