A novel lipoprotein lipase gene missense mutation in Chinese patients with severe hypertriglyceridemia and pancreatitis.

BACKGROUND: Alterations or mutations in the lipoprotein lipase (LPL) gene contribute to severe hypertriglyceridemia (HTG). This study reported on two patients in a Chinese family with LPL gene mutations and severe HTG and acute pancreatitis. METHODS: Two patients with other five family members were included in this study for DNA-sequences of hyperlipidemia-related genes (such as LPL, APOC2, APOA5, LMF1, and GPIHBP1) and 43 healthy individuals and 70 HTG subjects were included for the screening of LPL gene mutations. RESULTS: Both patients were found to have a compound heterozygote for a novel LPL gene mutation (L279V) and a known mutation (A98T). Furthermore, one HTG subject out of 70 was found to carry this novel LPL L279V mutation. CONCLUSIONS: The data from this study showed that compound heterozygote mutations of A98T and L279V inactivate lipoprotein lipase enzymatic activity and contribute to severe HTG and acute pancreatitis in two Chinese patients. Further study will investigate how these LPL gene mutations genetically inactivate the LPL enzyme.

Genetic Variants Associated with Gestational Hypertriglyceridemia and Pancreatitis.

Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis.

Abdominal lymphangiomatosis in a 38-year-old female: case report and literature review.

Lymphangioma is an uncommon benign tumor that develops in the lymphatic system. Abdominal lymphangiomatosis is extremely rare in adult patients, and the clinical symptoms of this condition are complicated and atypical. We report a case of abdominal lymphangiomatosis in a 38-year-old female who presented with intestinal bleeding and protein-losing enteropathy, as well as lesions in the lung and bones. A computed tomography scan revealed multiple small cystic lesions without enhancement. Histological examination revealed microscopic cysts were submucosal, with walls composed of thin fibrous tissue, and D2-40 stained highlight the lining of the lymphatic channels by immunohistochemical method. We make a comparison with the cases reported before, and also discuss the diagnose of diffuse pulmonary lymphangiomatosis and Gorham's disease.

Correlation of fibrinogen-like protein 2 with progression of acute pancreatitis in rats.

AIM: To examine fibrinogen-like protein 2 (fgl2) expression during taurocholate-induced acute pancreatitis progression in rats and its correlation with pancreatic injury severity. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into the severe acute pancreatitis (SAP) group (n = 24) and the sham operation (SO) group (n = 24). Sodium taurocholate (4% at doses of 1 mL/kg body weight) was retrogradely injected into the biliopancreatic ducts of the rats to induce SAP. Pancreatic tissues were prepared immediately after sacrifice. At the time of sacrifice, blood was obtained for determination of serum amylase activity and isolation of peripheral blood mononuclear cells (PBMCs). Pancreatic tissue specimens were obtained for routine light microscopy including hematoxylin and eosin staining, and the severity of pancreatic injury was evaluated 1, 4 and 8 h after induction. Expression of fgl2 mRNA was measured in the pancreas and PBMCs using reverse transcription polymerase chain reaction. Expression of fgl2 protein was evaluated in pancreatic tissues using Western blotting and immunohistochemical staining. Masson staining was also performed to observe microthrombosis. RESULTS: At each time point, levels of fgl2 mRNAs in pancreatic tissues and PBMCs were higher (P < 0.05) in the SAP group than in the SO group. For pancreatic tissue in SAP vs SO, the levels were: after 1 h, 3.911 ± 1.277 vs 1.000 ± 0.673; after 4 h, 9.850 ± 3.095 vs 1.136 ± 0.609; and after 8 h, 12.870 ± 3.046 vs 1.177 ± 0.458. For PBMCs in SAP vs SO, the levels were: after 1 h, 2.678 ± 1.509 vs 1.000 ± 0.965; after 4 h, 6.922 ± 1.984 vs 1.051 ± 0.781; and after 8 h, 13.533 ± 6.575 vs 1.306 ± 1.179. Levels of fgl2 protein expression as determined by Western blotting and immunohistochemical staining were markedly up-regulated (P < 0.001) in the SAP group compared with those in the SO group. For Western blotting in SAP vs SO, the results were: after 1 h, 2.183 ± 0.115 vs 1.110 ± 0.158; after 4 h, 2.697 ± 0.090 vs 0.947 ± 0.361; and after 8 h, 3.258 ± 0.094 vs 1.208 ± 0.082. For immunohistochemical staining in SAP vs SO, the results were: after 1 h, 1.793 ± 0.463 vs 0.808 ± 0.252; after 4 h, 4.535 ± 0.550 vs 0.871 ± 0.318; and after 8 h, 6.071 ± 0.941 vs 1.020 ± 0.406. Moreover, we observed a positive correlation in the pancreas (r = 0.852, P < 0.001) and PBMCs (r = 0.735, P < 0.001) between fgl2 expression and the severity of pancreatic injury. Masson staining showed that microthrombosis (%) in rats with SAP was increased (P < 0.001) compared with that in the SO group and it was closely correlated with fgl2 expression in the pancreas (r = 0.842, P < 0.001). For Masson staining in SAP vs SO, the results were: after 1 h, 26.880 ± 9.031 vs 8.630 ± 3.739; after 4 h, 53.750 ± 19.039 vs 8.500 ± 4.472; and after 8 h, 80.250 ± 12.915 vs 10.630 ± 7.003. CONCLUSION: Microthrombosis due to fgl2 overexpression contributes to pancreatic impairment in rats with SAP, and fgl2 level may serve as a biomarker during early stages of disease.

Use of artificial neural network to predict esophageal varices in patients with HBV related cirrhosis.

BACKGROUND: Prediction of esophageal varices in cirrhotic patients by noninvasive methods is still unsatisfactory. OBJECTIVES: To evaluate the accuracy of an artificial neural network (ANN) in predicting varices in patients with HBV related cirrhosis. PATIENTS AND METHODS: An ANN was constructed with data taken from 197 patients with HBV related cirrhosis. The candidates for input nodes of the ANN were assessed by univariate analysis and sensitivity analysis. Five-fold cross validation was performed to avoid over-fitting. RESULTS: 14 variables were reduced by univariate and sensitivity analysis, and an ANN was developed with three variables (platelet count, spleen width and portal vein diameter). With a cutoff value of 0.5. The ANN model has a sensitivity of 96.5%, specificity of 60.4%, positive predictive value of 86.9%, negative predictive value of 86.5% and a diagnostic accuracy of 86.8% for the prediction of varices. CONCLUSIONS: An ANN may be useful for predicting presence of esophageal varices in patients with HBV related cirrhosis.