Rare and common variants in LPL and APOA5 in Thai subjects with severe hypertriglyceridemia: A resequencing approach

Khovidhunkit, Weerapan; Charoen, Supannika; Kiateprungvej, Arunrat; Chartyingcharoen, Palm; Muanpetch, Suwanna; Plengpanich, Wanee

doi:10.1016/j.jacl.2015.11.007

Cited by 25 publications

(33 citation statements)

References 31 publications

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“…Although the p.G185C variant located in the APOA5 gene was first reported in 2003, it has attracted great attention from researchers during the past years because its homozygous mutation contributes strongly to severe hypertriglyceridemia and resultant HTGAP . In particular, the p.G185C polymorphism in the APOA5 gene is more commonly distributed in Asians, including Chinese populations, than in others . It has been speculated that the functional mechanism of APOA5 can decrease the concentration of blood TG by increasing lipoprotein lipase activity .…”

Section: Discussionmentioning

confidence: 99%

“…We thus conducted a retrospective study on AP patients who were admitted to our emergency department between 2012 and 2016, focusing on HTGAP. Considering that notable dyslipidemias have a strong genetic component despite the important role that secondary dietary factors play in the clinical phenotype, we further performed gene mutation detection for 11 patients with HTGAP to determine the molecular genetic characteristics of this special subtype of AP . In this study, we aimed to predict the severity and recurrence risk in HTGAP with the new‐generation sequencing techonology based upon clinical information of the patients.…”

Section: Introductionmentioning

confidence: 99%

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Hypertriglyceridemic acute pancreatitis in emergency department: Typical clinical features and genetic variants

Chen

Sun

Zhang

et al. 2017

J of Digest Diseases

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OBJECTIVE:To investigate the clinical characteristics of patients with hypertriglyceridemic acute pancreatitis (HTGAP), and the molecular foundation contributing to hypertriglyceridemia in such patients. METHODS:Clinical data from 329 patients with acute pancreatitis (AP) were analyzed. The patients were divided into the HTGAP group, with fasting serum triglyceride (TG) levels ≥500 mg/dL (5.65 mmol/L), and the non-HTGAP (NHTGAP) group. Targeted next-generation sequencing was applied to 11 HTGAP patients to identify the genetic mutations associated with hypertriglyceridemia, including apolipoprotein A-V (APOA5), APOC2, APOC3 and APOE, BLK, LPL, GPIHBP1 and LMF1. RESULTS:Patients in the HTGAP group, compared with those in the NHTGAP group, had a higher mortality rate (7.5% vs 0.7%, P = 0.001), more commonly seen severe AP (17.5% vs 5.2%, P = 0.004) as well as a higher recurrence rate (32.4% vs 19.9%, P = 0.070). DNA sequencing showed that two patients carried the same compound of p.G185C and p.V153M heterozygous mutations located in the APOA5 gene. Two patients carried a homozygous variation of p.C14F, in the GPIHBP1 gene. One patient had a homozygous variation of p.R176C in the APOE gene. And a rare heterozygous LMF1 gene mutation of p.P562R was detected in two patients.CONCLUSIONS: HTGAP was significantly severe than NHTGAP, with a high recurrence rate. Genetic information may be useful in the clinical setting for the investigation of the pathogenesis of HTGAP and its interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypertriglyceridemic acute pancreatitis in emergency department: Typical clinical features and genetic variants

Chen

Sun

Zhang

et al. 2017

J of Digest Diseases

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“…Recently, Weerapan et al resequenced the LPL gene in 101 individuals with hypertriglyceridemia and 111 normotriglyceridemic controls and found six rare variants in the coding region of LPL. All these known variants, p.Ala98Thr, p.Leu279Val, and p.Leu279Arg, have been associated with severe hypertriglyceridemia.…”

Section: Discussionmentioning

confidence: 99%

Rare LPL gene missense mutation in an infant with hypertriglyceridemia

Qin

Wei

Shan

et al. 2018

Clinical Laboratory Analysis

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“…1,3,4 In addition, patients with fasting TG level in between 1000 (11.3 mmol/L) and 2000 mg/dL (22.6 mmol/L) are diagnosed as 'severe HTG', carrying increased risk of developing pancreatitis as TG level may rise above 2000 mg/dL (22.6 mmol/L) after eating. 8,9 According to the aetiology, HTG is classified into two types, primary and secondary. [5][6][7] However, the specific mechanism by which HTG patients gradually develop AP is still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Severe HTG patients with serum TG level >11.3 mmol/L (1000 mg/dL) gradually and progressively developed hepatosplenomegaly, stomach ache, lipaemia retinalis and eruptive xanthomas with an increased risk of AP. 9 In addition, primary HTG is usually caused by germline mutations of lipoprotein lipase (LPL) gene. One obvious explanation is that both HTG and increased level of chylomicrons (CM) lead to increase the plasma viscosity, which leads to ischaemia in pancreatic tissue and organ inflammation.…”

Section: Introductionmentioning

confidence: 99%

Identification and functional characterization of mutations in LPL gene causing severe hypertriglyceridaemia and acute pancreatitis

Han

Wei

Cai

et al. 2020

J Cellular Molecular Medi

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Hypertriglyceridaemia is a very rare disorder caused by the mutations of LPL gene, with an autosomal recessive mode of inheritance. Here, we identified two unrelated Chinese patients manifested with severe hypertriglyceridaemia and acute pancreatitis. The clinical symptoms of proband 1 are more severe than proband 2. Whole exome sequencing and Sanger sequencing were performed. Functional analysis of the identified mutations has been done. Whole exome sequencing identified two pairs of variants in LPL gene in the proband 1 (c.162C>A and c.1322+1G>A) and proband 2 (c.835C>G and c.1322+1G>A). The substitution (c.162C>A) leads to the formation of a truncated (p.Cys54*) LPL protein. The substitution (c.835C>G) leads to the replacement of leucine to valine (p.Leu279Val). The splice donor site mutation (c.1322+1G>A) leads to the formation of alternative transcripts with the loss of 134 bp in exon 8 of the LPL gene. The proband 1 and his younger son also harbouring a heterozygous variant (c.553G>T; p.Gly185Cys) in APOA5 gene. The relative expression level of the mutated LPL mRNA (c.162C>A, c.835C>G and c.1322+1G>A) showed significant differences compared to wild-type LPL mRNA, suggesting that all these three mutations affect the transcription of LPL mRNA. These three mutations (c.162C>A, c.835C>G and c.1322+1G>A)showed noticeably decreased LPL activity in cell culture medium but not in cell lysates.Here, we identified three mutations in LPL gene which causes severe hypertriglyceridaemia with acute pancreatitis in Chinese patients. We also described the significance of whole exome sequencing for identifying the candidate gene and disease-causing mutation in patients with severe hypertriglyceridaemia and acute pancreatitis.

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Rare and common variants in LPL and APOA5 in Thai subjects with severe hypertriglyceridemia: A resequencing approach

Cited by 25 publications

References 31 publications

Hypertriglyceridemic acute pancreatitis in emergency department: Typical clinical features and genetic variants

Hypertriglyceridemic acute pancreatitis in emergency department: Typical clinical features and genetic variants

Rare LPL gene missense mutation in an infant with hypertriglyceridemia

Identification and functional characterization of mutations in LPL gene causing severe hypertriglyceridaemia and acute pancreatitis

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