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Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

ABSTRACT: BACKGROUND:Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. OBJECTIVES:The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). METHODS:The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293?T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. RESULTS:We identified a novel nonsense variant, p.Gln118* (c.351C?>?T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. CONCLUSIONS:Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP.

SUBMITTER: Li XY

PROVIDER: S-EPMC7140582 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

Li Xiao-Yao XY Pu Na N Chen Wei-Wei WW Shi Xiao-Lei XL Zhang Guo-Fu GF Ke Lu L Ye Bo B Tong Zhi-Hui ZH Wang Yu-Hui YH Liu George G Chen Jian-Min JM Yang Qi Q Li Wei-Qin WQ Li Jie-Shou JS

Lipids in health and disease 20200407 1

<h4>Background</h4>Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG.<h4>Objectives</h4>The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older ...[more]

PMID: 32264896

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Project description:Acute pancreatitis is a common disease with an annual incidence of between 5 and 80 people per 100,000 of the population. The two major etiological factors responsible for acute pancreatitis are alcohol and cholelithiasis (gallstones). The proportion of patients with pancreatitis caused by alcohol or gallstones varies markedly in different countries and regions. The incidence of acute alcoholic pancreatitis is considered to be associated with high alcohol consumption. Although the incidence of alcoholic pancreatitis is much higher in men than in women, there is no difference in sexes in the risk involved after adjusting for alcohol intake. Other risk factors include endoscopic retrograde cholangiopancreatography, surgery, therapeutic drugs, HIV infection, hyperlipidemia, and biliary tract anomalies. Idiopathic acute pancreatitis is defined as acute pancreatitis in which the etiological factor cannot be specified. However, several studies have suggested that this entity includes cases caused by other specific disorders such as microlithiasis. Acute pancreatitis is a potentially fatal disease with an overall mortality of 2.1%-7.8%. The outcome of acute pancreatitis is determined by two factors that reflect the severity of the illness: organ failure and pancreatic necrosis. About half of the deaths in patients with acute pancreatitis occur within the first 1-2 weeks and are mainly attributable to multiple organ dysfunction syndrome (MODS). Depending on patient selection, necrotizing pancreatitis develops in approximately 10%-20% of patients and the mortality is high, ranging from 14% to 25% of these patients. Infected pancreatic necrosis develops in 30%-40% of patients with necrotizing pancreatitis and the incidence of MODS in such patients is high. The recurrence rate of acute pancreatitis is relatively high: almost half the patients with acute alcoholic pancreatitis experience a recurrence. When the gallstones are not treated, the risk of recurrence in gallstone pancreatitis ranges from 32% to 61%. After recovering from acute pancreatitis, about one-third to one-half of acute pancreatitis patients develop functional disorders, such as diabetes mellitus and fatty stool; the incidence of chronic pancreatitis after acute pancreatitis ranges from 3% to 13%. Nevertheless, many reports have shown that most patients who recover from acute pancreatitis regain good general health and return to their usual daily routine. Some authors have emphasized that endocrine function disorders are a common complication after severe acute pancreatitis has been treated by pancreatic resection.

Dataset Information

Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

Publications

Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

Similar Datasets

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