The apolipoprotein C-II variant apoC-IILys19→Thr is not associated with dyslipidemia in an affected kindred

The rare apolipoprotein C-II (apoC-II) mutation, apoC-II_Lys19→Thr, also known as apoC-II-v, has been found previously in association with hyperlipoproteinemia. From a lipid clinic screening we identified three unrelated individuals who had the apoC-II_Lys19→Thr mutation. Among eight family members of one proband, we have found another four who were affected. None of the inviduals in this kindred is dyslipidemic and there is no difference in lipid levels between affected and unaffected family members. Therefore, we conclude that the presence of this apolipoprotein variant by itself has no effect on lipoprotein levels. In addition, the apolipoprotein E (apoE) isoform, apoE4 does not have a synergistic effect on lipoprotein levels in this kindred, in contrast to observations on the interaction of apoE4 with another apoC-II mutant (apoC-II_Toronto). The single nucleotide substitution that causes the apoC-II_Lys19→Thr variant introduces a previously unrecognized restriction site (for Mae III), that provides for easy screening.     

脂蛋白脂肪酶基因突变的研究

目的：筛查国人脂蛋白脂肪酶(LPL)基因的突变，并探讨其与高甘油三酯血症的关系。方法：对高甘油三酯血症组(48例)和正常甘油三酯对照组(121例)的各扩增片段进行分析，电泳图谱异常者进行PCR产物测序。对于频率较高的多态性位点，引入限制性核酸内切酶位点利用PCR-RFLP进行鉴定。结果：在高甘油三酯血症人群中，检出2例内含子3受位剪接点上游6bp的C→T转换的突变杂合子，1例外显子5Pm^207→Leu突变杂合子，在全部样品中检出1例Ser^447→stop突变纯合子，50例Ser^447→stop杂合子。结论：天津地区人群中存在着LPL基因突变，除Ser^447→stop外，内含子3和外显子5的突变多与高甘油三酯血症相关，可能是高甘油三酯血症的遗传易感因子。     

A 19 year follow‐up of a woman with lipoprotein lipase deficiency treated with biliopancreatic diversion

We show the long‐term efficacy and safety of modified biliopancreatic diversion for the treatment of LPL‐deficiency. How this option compares with gene therapy is difficult to evaluate due to limited experience. Surgery may be the first option in patients in whom medical therapy is ineffective and gene therapy not applicable.     

The effect of intravenous insulin,apheresis and oral lipid-lowering agents on non-fasting hypertriglyceridemia and associated pancreatitis

Objectives: There is evidence that increasing severity of hypertriglyceridemia increases the risk of acute pancreatitis. There is a debate about superiority of treatment methods and previous works have specifically called for direct comparison between IV insulin and apheresis techniques. Identify patient characteristics predictive of lipid-lowering therapy selection in a large community hospital for treatment of hypertriglyceridemia; evaluate for a concentration-dependent relationship between hypertriglyceridemia severity and risk of acute pancreatitis; assess for differences in clinical outcomes between patients treated with IV insulin versus apheresis.

Methods: Single center, retrospective cohort study including patients with hypertriglyceridemia between January 2007 and December 2016. Main measures included frequency of pancreatitis, choice of lipid-lowering therapy, and clinical comparisons of diet, oral lipid-lowering agents, IV insulin, and apheresis.

Results: Initial serum triglyceride level and disease acuity was higher among patients in insulin and apheresis groups. Neither triglyceride level, Charlson comorbidity index, age, BISAP score, nor initial CRP predicted use of IV insulin versus apheresis. Prevalence of pancreatitis increased with higher triglyceride level, reaching 48% with triglycerides >2000 md/dL (p < 0.001). There was a significant decrease in serum triglycerides at each time interval (p < 0.05) in patients treated with IV insulin and apheresis, but no difference in clearance rate between the two. Length of stay did not differ between IV insulin and apheresis.

Conclusion: The presence of pancreatitis, hyperglycemia, and hypertriglyceridemia severity influenced selection of therapies like IV insulin and apheresis. We found no superiority of either IV insulin or apheresis in the treatment of severe hypertriglyceridemia among patients hospitalized for pancreatitis.     

Release of nonesterified fatty acids during cerulein-induced pancreatitis in rats

During acute pancreatitis, data obtainedin vitro suggest that pancreatic lipase, acting on circulating or tissular triglycerides, might generate nonesterified fatty acids (NEFA) that could promote pancreatic and fat tissue necrosis. This work determined whether NEFA were actually producedin vivo in pancreatic tissue and in blood during cerulein-induced pancreatitis in rats. Intraperitoneal injections of cerulein induced pancreatitis. To promote the possible NEFA release by pancreatic lipase, a venous infusion of human very low density lipoprotein (VLDL) was used to cause hypertriglyceridemia. NEFA were measured in portal and aortic blood and in tissue extracts prepared from pancreas homogenates. NEFA did not increase either in peripheral or in portal blood. In pancreatic tissue, NEFA levels did not differ from controls. The major hypertriglyceridemia produced by human VLDL intravenous infusion neither altered the course of the disease nor promoted plasma NEFA release. The role commonly attributed to NEFA in acute pancreatitis seems questionable.Dr. Paye was the recipient of a scholarship from the Fondation pour la Recherche Médicale (Paris). Partial financial support of the work was provided by the Conseil Scientifique of Faculté X. Bichat and by Association Charles Debray.     

Hypertriglyceridemia: the importance of identifying patients at risk

This review aims to explain risk factors, consequences, and management strategies recommended for patients with hypertriglyceridemia. A search of PubMed was performed: ‘Hypertriglyceridemia’[Majr], limited to English‐language and published in the 5 years up to April 2016. Abstracts of the 680 results were screened for inclusion. Reference lists of publications included were also screened for inclusion.

Approximately 25% of the United States population has elevated (≥150 mg/dL) triglycerides (TG) putting them at an increased risk of cardiovascular disease, non-alcoholic fatty liver disease, and pancreatitis. Risk factors for hypertriglyceridemia include genetics, lifestyle and diet, renal disease, endocrine disorders, and certain medications. Guidelines recommend that all patients with hypertriglyceridemia are advised on lifestyle modification to reduce TG to <150 mg/dL; a reduction in body weight of 5–10% can reduce TG by approximately 20%. For patients with TG <400 mg/dL, the primary goal is to reduce low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol, with most guidelines recommending statin therapy. When TG is ≥500 mg/dL the primary goal is to reduce TG levels to lower the risk of pancreatitis. Statin therapy (if LDL-C is elevated) in combination with a fibrate, or long-chain omega-3 fatty acid may be required. The Food and Drug Administration withdrew approval for niacin and some fibrates in combination with statins in April 2016 citing unfavorable benefit-risk profiles. With the increasing incidence of associated conditions (e.g. obesity, metabolic syndrome, and type 2 diabetes mellitus), it is likely that primary care physicians will encounter more patients with hypertriglyceridemia.     

Physicochemical Changes in HDL3 after Bezafibrate Treatment: Influence on Free Cholesterol Efflux from Human Fibroblasts

The effects of bezafibrate, a well-used fibric acid hypolipidemic agent, were investigated in 10 moderately hypertriglyceridemic patients. The aim was to quantify the physico-chemical modifications to high-density lipoprotein subfraction 3 (HDL₃) induced by treatment and to assess, in vitro, the alterations in its principal physiological function, the efflux of intracellular free cholesterol. Treatment (200mg/thrice/d for 3 months) resulted in a 48% decrease in plasma triglycerides, with an increase in the HDL cholesterol, due mainly to an increase in the HDL₃ (P < 0.01). Composition analysis of HDL₃indicated an increase in cholesterol esters (P < 0.01), free cholesterol (P < 0.01), and phospholipids (P < 0.01), coupled with a decrease in the protein content of the molecule compared with pretreatment values. Fluorescense anisotropy at 24°C was significantly higher post-treatment than pretreatment (P < 0.01). The cholesterol effluxing capacity of pretreatment HDL₃ was 28%, and post-treatment this increased to 50% (P < 0.01). Multivariate analyses indicated that the increased capacity of HDL₃ to promote free cholesterol efflux was, in part, due to increased HDL₃ phospholipid content and a more adequate fluidity of the molecule. These findings suggest that bezafibrate induces a lowering of plasma triglycerides and that the resultant physico-chemical alterations of the HDL₃ molecule make it more efficient as an acceptor of intracellular free cholesterol. This revised version was published online in July 2006 with corrections to the Cover Date.     

苯扎贝特联合降压治疗对高血压合并高甘油三酯血症患者内皮功能和血压的影响

目的 用随机、对照的方法观察苯扎贝特联合降压治疗对高甘油三酯血症合并高血压患者内皮功能和血压的影响。方法 58例高甘油三酯血症伴原发性高血压患者随机分为苯扎贝特组(A组)和对照组(B组)，通过治疗前后血压、血脂、血浆内皮素(endothelin，ET)、一氧化氮(nitric oxide，NO)、血栓烷A2(thromboxane A2，TXA2)、前列环素I2(PGI2)和降钙素基因相关肽(calcitonin gene-related peptide，CGRP)等指标的变化，来观察苯扎贝特对患者血管内皮功能和血压的影响。结果 A组在治疗后血甘油三酯、总胆固醇、低密度脂蛋白胆固醇水平明显降低．高密度脂蛋白胆固醇显著升高；NO显著升高．ET、TXA2／PGI2明显降低；而且A组舒张压降低较B组显著，并与血甘油三酯水平及内皮功能的变化有关。结论 苯扎贝特可能通过调整血脂代谢紊乱，对患者的血管内皮功能有改善作用，并且在降压药物的基础上．可能对患者舒张压有额外降低作用．