A loss-of-function p.G191R variant in the anionic trypsinogen (PRSS2) gene in Japanese patients with pancreatic disorders
A loss-of-function p.G191R variant in the anionic trypsinogen (PRSS2) gene in Japanese patients with pancreatic disorders
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DOI：
10.1136/gut.2008.151688
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发表时间：
2009-06-01
期刊：
影响因子：
24.5
通讯作者：
Shimosegawa, T.
中科院分区：
文献类型：
--
作者：
Kume, K.;Masamune, A.;Shimosegawa, T.
目的：有一种观点认为，胰腺炎是由于胰腺实质内蛋白水解酶及其抑制物的失衡所致。最近有研究表明，在欧洲人群中，阴离子胰蛋白酶原(PRSS2)基因中的一个功能丧失的变体c.571G>；A(p.G191R)对慢性胰腺炎具有保护作用。方法：从378例健康对照和604例胰腺疾病患者(慢性胰腺炎241例，急性胰腺炎174例，胰腺肿瘤189例)中提取基因组DNA。结果：241例慢性胰腺炎患者中有3例(1.2%)存在pG191R杂合子突变，174例急性胰腺炎患者中有7例(4.0%)存在pG191R杂合子突变，189例胰腺肿瘤患者中有12例(6.3%)存在pG191R杂合突变。378例(6.6%)健康对照中有25例(2例为纯合子，23例为杂合子)发现了p.G191R突变。慢性胰腺炎患者的p.G191R频率低于健康对照组(p=0.001；优势比(OR)0.178；95%可信区间(CI)=0.057~0.561)。酒精性(0.9%；p=0.015；OR，0.132；95%CI，0.022~0.779)和特发性(1.0%；p=0.025；OR，0.144；95%CI，0.025~0.851)慢性胰腺炎患者的p.G191R频率低于健康对照组。在健康对照组和急性胰腺炎或胰腺肿瘤患者之间，p.G191R频率没有统计学差异。酒精性急性胰腺炎(n=59)患者无变异携带者，p.G191R频率低于健康对照组(p=0.035)。结论：p.G191R变异对日本酒精性和特发性慢性胰腺炎以及酒精性急性胰腺炎有保护作用。
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.