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基因中的遗传变异及其对急性胰腺炎风险的影响:一项大规模研究的新见解。

Genetic Variability in the Gene and Its Impact on Acute Pancreatitis Risk: New Insights from a Large-Scale Study.

机构信息

Department of Surgical Medicine with the Laboratory of Medical Genetics, Collegium Medicum, Jan Kochanowski University of Kielce, 25-317 Kielce, Poland.

Department of Mathematics, Jan Kochanowski University of Kielce, 25-406 Kielce, Poland.

出版信息

Int J Mol Sci. 2024 Oct 21;25(20):11301. doi: 10.3390/ijms252011301.

Abstract

Acute pancreatitis (AP) is a common and potentially lethal disease. Over the last 10 years, AP has become one of the most important healthcare problems. On a global scale, the incidence has increased by 63% over the last 20 years. AP is usually caused by gallstones and excessive alcohol consumption and genetic factors play an important role in the development of inflammation. Recent studies involving the mutations are ambiguous and dependent on the population studied. In this study, the variability of the gene in patients with AP was analyzed. Genetic material was isolated from the blood of 301 patients with AP and 184 healthy individuals. Identification of the variants in exons 5, 6, 8, and 9 with introns was performed using molecular biology methods. Mutations were identified by comparison to the reference sequence (NM_001868.4). Statistical analysis included the identification of mutations correlating with the risk of AP, the etiology of inflammation, and family history. Several novel mutations in the gene have been identified, along with a high degree of variability within the coding region of the carboxypeptidase gene. A correlation between mutations :c.1072 + 84del; c.987 + 57G>A and increased risk of developing AP was found. Two protective mutations, :c.625A>T, c.1072 + 94del, were identified. The gene is characterized by high sequence variability and regions in which mutations lead to an increased risk of developing AP. Single or co-occurring mutations of the gene can significantly affect the risk of developing AP.

摘要

急性胰腺炎(AP)是一种常见且潜在致命的疾病。在过去的 10 年中,AP 已成为最重要的医疗保健问题之一。在全球范围内,过去 20 年的发病率增加了 63%。AP 通常由胆结石和过度饮酒引起,遗传因素在炎症的发展中起着重要作用。最近涉及基因的研究结果并不明确,且取决于所研究的人群。在这项研究中,分析了 AP 患者中基因的变异性。从 301 名 AP 患者和 184 名健康个体的血液中分离出遗传物质。使用分子生物学方法对第 5、6、8 和 9 外显子与内含子的变异进行了鉴定。通过与参考序列(NM_001868.4)进行比较来鉴定突变。统计分析包括鉴定与 AP 风险、炎症病因和家族史相关的突变。已经鉴定出该基因中的几个新突变,以及羧肽酶基因编码区的高度变异性。发现突变:c.1072 + 84del;c.987 + 57G>A 与 AP 发病风险增加之间存在相关性。鉴定出两个保护性突变:c.625A>T,c.1072 + 94del。该基因的特点是序列高度变异,并且突变导致 AP 发病风险增加的区域。基因的单突变或共突变可显著影响 AP 的发病风险。

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