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Witt H.,TU Munich | Beer S.,Boston University | Rosendahl J.,University of Leipzig | Chen J.-M.,French Institute of Health and Medical Research | And 80 more authors.
Nature Genetics

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. unctionally 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. © 2013 Nature America, Inc. All rights reserved. Source

Hauner H.,TU Munich | Hauner H.,Zentralinstitut For Ernahrungs Und Lebensmittelforschung Ziel | Much D.,TU Munich | Vollhardt C.,TU Munich | And 12 more authors.
American Journal of Clinical Nutrition

Background: The composition of long-chain PUFAs (LCPUFAs) in the maternal diet may affect obesity risk in the mother's offspring. Objective: We hypothesized that a reduction in the n-6 (omega-6): n-3 (omega-3) LCPUFA ratio in the diet of pregnant women and breastfeeding mothers may prevent expansive adipose tissue growth in their infants during the first year of life. Design: In a randomized controlled trial, 208 healthy pregnant women were randomly assigned to an intervention (1200 mg n-3 LCPUFAs as a supplement per day and a concomitant reduction in arachidonic acid intake) or a control diet from the 15th wk of pregnancy to 4 mo of lactation. The primary outcome was infant fat mass estimated by skinfold thickness (SFT) measurements at 4 body sites at 3-5 d, 6 wk, and 4 and 12 mo postpartum. Secondary endpoints included sonographic assessment of abdominal subcutaneous and preperitoneal fat, fat distribution, and child growth. Results: Infants did not differ in the sum of their 4 SFTs at ≤1 y of life [intervention: 24.1 ± 4.4 mm (n = 85); control: 24.1 ± 4.1 mm (n = 80); mean difference: -0.0 mm (95% CI: -1.3, 1.3 mm)] or in growth. Likewise, longitudinal ultrasonography showed no significant differences in abdominal fat mass or fat distribution. Conclusions: We showed no evidence that supplementation with n-3 fatty acids and instructions to reduce arachidonic acid intake during pregnancy and lactation relevantly affects fat mass in offspring during the first year of life. Prospective long-term studies are needed to explore the efficacy of this dietary approach for primary prevention. This trial was registered at clinicaltrials.gov as NCT00362089. © 2012 American Society for Nutrition. Source

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