日本胰腺疾病患者阴离子胰蛋白酶原（PRSS2）基因中的功能丧失性p.G191R变体。

A loss-of-function p.G191R variant in the anionic trypsinogen (PRSS2) gene in Japanese patients with pancreatic disorders.

作者信息

Kume K, Masamune A, Takagi Y, Kikuta K, Watanabe T, Satoh K, Satoh A, Hirota M, Hamada S, Shimosegawa T

机构信息

Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 Japan.

出版信息

Gut. 2009 Jun;58(6):820-4. doi: 10.1136/gut.2008.151688. Epub 2008 Dec 3.

DOI:10.1136/gut.2008.151688

PMID:19052022

Abstract

OBJECTIVE

There is a concept that pancreatitis results from an imbalance of proteases and their inhibitors within the pancreatic parenchyma. It has been recently shown that a loss-of-function variant, c.571G>A (p.G191R), in the anionic trypsinogen (PRSS2) gene protects against chronic pancreatitis in European populations. Here we examined the association of the p.G191R variant with pancreatic disorders in Japan.

METHODS

Genomic DNA was prepared from 378 healthy controls and 604 patients with pancreatic disorders (241 patients with chronic pancreatitis, 174 with acute pancreatitis, and 189 with pancreatic neoplasm). Mutational analysis of the PRSS2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing.

RESULTS

The heterozygous p.G191R variant was found in three of 241 (1.2%) patients with chronic pancreatitis, in seven of 174 (4.0%) patients with acute pancreatitis, and in 12 of 189 (6.3%) patients with pancreatic neoplasm. The p.G191R variant was found in 25 (two were homozygous and 23 were heterozygous) of 378 (6.6%) healthy controls. The p.G191R frequency in patients with chronic pancreatitis was lower than that in healthy controls (p = 0.001; odds ratio (OR) 0.178; 95% confidence interval (CI) = 0.057 to 0.561). The p.G191R frequency was lower in patients with alcoholic (0.9%; p = 0.015; OR, 0.132; 95% CI, 0.022 to 0.779) and idiopathic (1.0%; p = 0.025; OR, 0.144; 95% CI, 0.025 to 0.851) chronic pancreatitis than that in healthy controls. There were no statistical differences in the p.G191R frequency between healthy controls and patients with acute pancreatitis or with pancreatic neoplasm. Patients with alcoholic acute pancreatitis (n = 59) had no variant carrier, and the p.G191R frequency was lower than that in healthy controls (p = 0.035).

CONCLUSION

The p.G191R variant protected against alcoholic and idiopathic chronic pancreatitis as well as alcoholic acute pancreatitis in Japan.

摘要

目的

有一种观点认为胰腺炎是由胰腺实质内蛋白酶及其抑制剂失衡所致。最近研究表明，阴离子胰蛋白酶原（PRSS2）基因中的功能丧失变异c.571G>A（p.G191R）可预防欧洲人群的慢性胰腺炎。在此，我们研究了p.G191R变异与日本胰腺疾病的相关性。

方法

从378名健康对照者和604例胰腺疾病患者（241例慢性胰腺炎患者、174例急性胰腺炎患者和189例胰腺肿瘤患者）中提取基因组DNA。采用聚合酶链反应-限制性片段长度多态性和直接测序法对PRSS2基因进行突变分析。

结果

在241例慢性胰腺炎患者中有3例（1.2%）发现杂合p.G191R变异，174例急性胰腺炎患者中有7例（4.0%）发现该变异，189例胰腺肿瘤患者中有12例（6.3%）发现该变异。在378名健康对照者中有25例（2例纯合子和23例杂合子，占6.6%）发现p.G191R变异。慢性胰腺炎患者中p.G191R变异频率低于健康对照者（p = 0.001；优势比（OR）0.178；95%置信区间（CI） = 0.057至0.561）。酒精性（0.9%；p = 0.015；OR，0.132；95% CI，0.022至0.779）和特发性（1.0%；p = 0.025；OR，0.144；95% CI，0.025至0.851）慢性胰腺炎患者中p.G191R变异频率低于健康对照者。健康对照者与急性胰腺炎患者或胰腺肿瘤患者之间的p.G191R变异频率无统计学差异。酒精性急性胰腺炎患者（n = 59）中无变异携带者，其p.G191R变异频率低于健康对照者（p = 0.035）。