Department of Hepatology and Gastroenterology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany.
Pancreas. 2010 Mar;39(2):188-92. doi: 10.1097/MPA.0b013e3181bd94ae.
Premature activation of pancreatic digestive enzymes is considered as a major factor in the pathogenesis of pancreatitis. Genetic alterations of different pancreatic zymogens or their inhibitors have been associated with chronic pancreatitis (CP).
We sequenced all 12 GP2 exons in 380 German CP patients and in 182 German control subjects. In addition, we analyzed exon 3 of GP2 in 803 further CP patients and 1780 controls originating from Germany, the Netherlands, and India by targeted DNA sequencing.
We detected 12 nonsynonymous and 6 synonymous exonic variants. All nonsynonymous changes with exception of c.220C>T (p.R74X) and c.502_503delG (p.G168fsX174) in exon 3 and c.541C>T (p.R181X) in exon 4 were missense mutations and predominantly located in exon 3. All nonsynonymous variants were found in single cases only, with exception of 2 alterations, c.355A>G (p.M119V) and c.409G>A (p. A137T), both located in exon 3. To elucidate the role of these 2 exon 3 variants, we investigated additional patients and controls. The frequency of these variants was similar between patients and controls regardless of ethnic background or cause of CP.
Our data suggest that GP2 alterations do not alter the risk for the development of CP.
胰脏消化酶的过早激活被认为是胰腺炎发病机制中的一个主要因素。不同胰脏酶原或其抑制剂的遗传改变与慢性胰腺炎（CP）有关。
我们对 380 名德国 CP 患者和 182 名德国对照者的所有 12 个 GP2 外显子进行了测序。此外，我们通过靶向 DNA 测序分析了来自德国、荷兰和印度的 803 名进一步的 CP 患者和 1780 名对照者的 GP2 外显子 3。
我们检测到 12 个非同义突变和 6 个同义突变。除了外显子 3 中的 c.220C>T（p.R74X）和 c.502_503delG（p.G168fsX174）以及外显子 4 中的 c.541C>T（p.R181X）外，所有非同义变化均为错义突变，且主要位于外显子 3 中。所有非同义突变仅在单个病例中发现，除了 2 个位于外显子 3 的改变 c.355A>G（p.M119V）和 c.409G>A（p. A137T）外。为了阐明这两个外显子 3 变体的作用，我们对额外的患者和对照者进行了研究。无论种族背景或 CP 的病因如何，这些变体的频率在患者和对照者之间相似。
我们的数据表明，GP2 改变不会改变 CP 发展的风险。
