期刊
NATURE GENETICS
卷 45, 期 10, 页码 1216-U359出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2730
关键词
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资金
- Deutsche Forschungsgemeinschaft (DFG) [Wi 2036/2-2, Wi 2036/2-3, RO 3929/1-1, RO 3939/2-1]
- Else Kroner-Fresenius-Foundation (EKFS)
- Colora Stiftung gGmbH
- US National Institutes of Health (NIH) [R01DK058088, R01DK082412, R01DK082412-S2, R01DK095753]
- Rosztoczy Foundation
- Hungarian Academy of Sciences
- INSERM
- Programme Hospitalier de Recherche Clinique [PHRC R 08-04]
- French Association des Pancreatites Chroniques Hereditaires
- Czech Ministry of Health conceptual development project of research organization University Hospital Motol in Prague [00064203]
- Council of Scientific and Industrial Research (CSIR), Ministry of Science and Technology, Government of India, India
- Japan Society for the Promotion of Science [23591008]
- Research Committee of Intractable Pancreatic Diseases by the Ministry of Health, Labour and Welfare of Japan
- [CZ.2.16/3.1.00/24022OPPK]
- Grants-in-Aid for Scientific Research [23591008] Funding Source: KAKEN
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 x 10(-16)). The association was strongest in subjects aged = 10 years (9.7%; OR = 84.0, P = 4.1 x 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.
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