Center for Exocrine Disorders, Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA, United States of America.
First Department of Medicine, University of Szeged, Szeged, Hungary.
PLoS One. 2018 Nov 8;13(11):e0206869. doi: 10.1371/journal.pone.0206869. eCollection 2018.
A nonsense variant (p.W358X) of human pancreatic lipase related protein 2 (PNLIPRP2) is present in different ethnic populations with a high allele frequency. In cell culture experiments, the truncated protein mainly accumulates inside the cells and causes endoplasmic reticulum stress. Here, we tested the hypothesis that variant p.W358X might increase risk for chronic pancreatitis through acinar cell stress. We sequenced exon 11 of PNLIPRP2 in a cohort of 256 subjects with chronic pancreatitis (152 alcoholic and 104 non-alcoholic) and 200 controls of Hungarian origin. We observed no significant difference in the distribution of the truncation variant between patients and controls. We analyzed mRNA expression in human pancreatic cDNA samples and found the variant allele markedly reduced. We conclude that the p.W358X truncation variant of PNLIPRP2 is expressed poorly and has no significant effect on the risk of chronic pancreatitis.
人类胰腺脂肪酶相关蛋白 2（PNLIPRP2）的无义变异体（p.W358X）存在于具有高等位基因频率的不同种族人群中。在细胞培养实验中，截短的蛋白质主要在细胞内积累并导致内质网应激。在这里，我们通过腺泡细胞应激测试了变体 p.W358X 可能增加慢性胰腺炎风险的假设。我们对 256 名慢性胰腺炎患者（152 名酒精性和 104 名非酒精性）和 200 名匈牙利裔对照者的 PNLIPRP2 第 11 外显子进行了测序。我们没有观察到患者和对照组之间截断变体分布的显著差异。我们分析了人胰腺 cDNA 样本中的 mRNA 表达，发现变体等位基因明显减少。我们得出结论，PNLIPRP2 的 p.W358X 截断变体表达不佳，对慢性胰腺炎的风险没有显著影响。
