CPA1 中的变异与早发性慢性胰腺炎密切相关。
Variants in CPA1 are strongly associated with early onset chronic pancreatitis.
机构信息
1] Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München (TUM), Freising, Germany. [2] Zentralinstitut für Ernährungs- und Lebensmittelforschung (ZIEL), TUM, Freising, Germany. [3] Department of Pediatrics, Klinikum Rechts der Isar (MRI), TUM, Munich, Germany.
出版信息
Nat Genet. 2013 Oct;45(10):1216-20. doi: 10.1038/ng.2730. Epub 2013 Aug 18.
Chronic pancreatitis is an inflammatory disorder of the pancreas. We analyzed CPA1, encoding carboxypeptidase A1, in subjects with nonalcoholic chronic pancreatitis (cases) and controls in a German discovery set and three replication sets. Functionally impaired variants were present in 29/944 (3.1%) German cases and 5/3,938 (0.1%) controls (odds ratio (OR) = 24.9, P = 1.5 × 10(-16)). The association was strongest in subjects aged ≤ 10 years (9.7%; OR = 84.0, P = 4.1 × 10(-24)). In the replication sets, defective CPA1 variants were present in 8/600 (1.3%) cases and 9/2,432 (0.4%) controls from Europe (P = 0.01), 5/230 (2.2%) cases and 0/264 controls from India (P = 0.02) and 5/247 (2.0%) cases and 0/341 controls from Japan (P = 0.013). The mechanism by which CPA1 variants confer increased pancreatitis risk may involve misfolding-induced endoplasmic reticulum stress rather than elevated trypsin activity, as is seen with other genetic risk factors for this disease.
慢性胰腺炎是一种胰腺的炎症性疾病。我们在德国发现组和三个复制组中分析了非酒精性慢性胰腺炎（病例）和对照个体中的 CPA1（编码羧肽酶 A1）。在 944 名德国病例中有 29 名（3.1%）和 3938 名对照中有 5 名（0.1%）存在功能受损的变异体（比值比（OR）=24.9，P=1.5×10(-16)）。在年龄≤10 岁的受试者中，相关性最强（9.7%；OR=84.0，P=4.1×10(-24)）。在复制组中，来自欧洲的 600 名病例中有 8 名（1.3%）和 2432 名对照中有 9 名（0.4%）（P=0.01）、来自印度的 230 名病例中有 5 名（2.2%）和 264 名对照中有 0 名（P=0.02）、来自日本的 247 名病例中有 5 名（2.0%）和 341 名对照中有 0 名（P=0.013）存在缺陷的 CPA1 变异体。CPA1 变异体增加胰腺炎风险的机制可能涉及错误折叠诱导的内质网应激，而不是像其他遗传风险因素那样导致该疾病的胰蛋白酶活性升高。
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