Sequence analysis of the 5′ region of the chymotrypsin C (CTRC) gene in chronic pancreatitis

IF 2.8 2区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Pancreatology Pub Date : 2025-02-01 DOI:10.1016/j.pan.2024.12.020

Zain A. Karamya , Regina Stefanovics , Máté Sándor , Réka Madarász , Adrienn Nagy , Andrea Szentesi , Péter Hegyi , László Czakó , Balázs Csaba Németh

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引用次数: 0

Abstract

Background/objectives

Loss-of-function chymotrypsin C (CTRC) variants increase the risk for chronic pancreatitis (CP) by reducing protective pancreatic CTRC activity. Variants in the 5’ upstream region that includes the promoter might affect CTRC expression but have not been investigated to date. The aim of the present study was to address this knowledge gap.

Methods

We analyzed ∼1.4 kb of the 5’ region of the CTRC gene in 293 patients with chronic pancreatitis of alcoholic and non-alcoholic etiology and 402 controls from the Hungarian National Pancreas Registry by direct Sanger sequencing.

Results

We identified 14 gene variants, which included 11 novel variants and 3 previously reported variants. When allele frequencies were considered, none of the variants were significantly overrepresented in CP cases or controls. Genotype distribution of the frequently occurring variant c.-913A>G showed a statistically significant enrichment of the homozygous GG genotype (versus the AA genotype) in CP cases versus controls (OR 1.67, 95 % CI 1.2–2.4, P 0.0053). However, the disease association was driven by the linkage disequilibrium with the known CTRC risk variant c.180C>T.

Conclusions

We found no significant association between variants in the 5’ region of the CTRC gene and CP risk.

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慢性胰腺炎凝乳胰蛋白酶C （CTRC）基因5 '区序列分析

背景/目的功能缺失的胰凝乳蛋白酶C （CTRC）变异通过降低胰腺保护性CTRC活性增加慢性胰腺炎（CP）的风险。包含启动子的5 '上游区域的变异可能会影响CTRC的表达，但迄今为止尚未研究过。本研究的目的是解决这一知识差距。方法：通过直接Sanger测序，我们分析了来自匈牙利国家胰腺登记处的293例酒精性和非酒精性慢性胰腺炎患者和402例对照者的CTRC基因5 '区约1.4 kb。结果共鉴定出14个基因变异，包括11个新变异和3个先前报道的变异。当考虑等位基因频率时，没有一个变异在CP病例或对照中显着过度代表。常见变异c - 913a>；G的基因型分布显示，与对照组相比，CP病例的纯合GG基因型（相对于AA基因型）显著富集（OR 1.67, 95% CI 1.2 ~ 2.4, P 0.0053）。然而，疾病关联是由已知CTRC风险变异c.180C>；T的连锁不平衡驱动的。结论：我们发现CTRC基因5′区变异与CP风险无显著相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pancreatology 医学-胃肠肝病学

CiteScore

7.20

自引率

5.60%

发文量

194

审稿时长

44 days

期刊介绍： Pancreatology is the official journal of the International Association of Pancreatology (IAP), the European Pancreatic Club (EPC) and several national societies and study groups around the world. Dedicated to the understanding and treatment of exocrine as well as endocrine pancreatic disease, this multidisciplinary periodical publishes original basic, translational and clinical pancreatic research from a range of fields including gastroenterology, oncology, surgery, pharmacology, cellular and molecular biology as well as endocrinology, immunology and epidemiology. Readers can expect to gain new insights into pancreatic physiology and into the pathogenesis, diagnosis, therapeutic approaches and prognosis of pancreatic diseases. The journal features original articles, case reports, consensus guidelines and topical, cutting edge reviews, thus representing a source of valuable, novel information for clinical and basic researchers alike.