Genotype-phenotype studies of six novelLPL mutations in Chinese patients with hypertriglyceridemia

Chan, Lisa; Lam, Ching‐Wan; Mak, Y. T.; Tomlinson, Brian; Tsang, Man-Woo; Baum, Larry; Masarei, J.R.L.; Pang, Chi‐Pui

doi:10.1002/humu.9054

Cited by 18 publications

(15 citation statements)

References 32 publications

(25 reference statements)

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“…These three genes play an important role in lipid metabolism and all function as anti T2D3138394041 and a reduction of these three genes contributes to the metabolic dysfunction and its associated disorders as consequences. However, all these three genes were down-regulated upon SPION treatment.…”

Section: Discussionmentioning

confidence: 99%

Superparamagnetic iron oxide nanoparticles alter expression of obesity and T2D-associated risk genes in human adipocytes

Sharifi

Daghighi

Motazacker

et al. 2013

Sci Rep

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Adipocytes hypertrophy is the main cause of obesity and its affliction such as type 2 diabetes (T2D). Since superparamagnetic iron oxide nanoparticles (SPIONs) are used for a wide range of biomedical/medical applications, we aimed to study the effect of SPIONs on 22 and 29 risk genes (Based on gene wide association studies) for obesity and T2D in human adipocytes. The mRNA expression of lipid and glucose metabolism genes was changed upon the treatment of human primary adipocytes with SPIONs. mRNA of GULP1, SLC30A8, NEGR1, SEC16B, MTCH2, MAF, MC4R, and TMEM195 were severely induced, whereas INSIG2, NAMPT, MTMR9, PFKP, KCTD15, LPL and GNPDA2 were down-regulated upon SPIONs stimulation. Since SEC16B gene assist the phagocytosis of apoptotic cells and this gene were highly expressed upon SPIONs treatment in adipocytes, it is logic to assume that SPIONs may play a crucial role in this direction, which requires more consideration in the future.

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Section: Discussionmentioning

confidence: 99%

Superparamagnetic iron oxide nanoparticles alter expression of obesity and T2D-associated risk genes in human adipocytes

Sharifi

Daghighi

Motazacker

et al. 2013

Sci Rep

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“…The first case report of L279 V was a heterozygous Hong Kong Chinese patient reported by Chan L et al [ 11 ]. Then, some population studies reported that the frequency of L279 V varied from 1/160 to 5/101 in Asian countries, such as Thailand, Mainland China, Taiwan and Hong Kong [ 5 , 11 , 12 , 24 – 27 ]. But in European continental ancestry groups, L279 V has never been reported, which may suggest that genetic variations in LPL differ between different races and ethnic backgrounds.…”

Section: Discussionmentioning

confidence: 99%

“…L279 V is a disease-causing missense change with LPL deficiency only among Asian patients, probably because of the founder effect [ 5 , 24 ]. L279 V has been verified to be pathogenic by both biomedical methods and in vitro studies, such as transfecting wild-type and L279 V LPL plasmids into COS-1 cells [ 11 , 27 ]. However, there has been no in vivo research to analyze its particular pathogenic mechanism.…”

Section: Discussionmentioning

confidence: 99%

Compound but non-linked heterozygous p.W14X and p.L279 V LPL gene mutations in a Chinese patient with long-term severe hypertriglyceridemia and recurrent acute pancreatitis

Yang

Shi

et al. 2018

Lipids Health Dis

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BackgroundVariants in the lipoprotein lipase (LPL), apolipoprotein C-II (APOC2), apolipoprotein A-V (APOA5), GPIHBP1 and LMF1 genes may cause severe hypertriglyceridemia (HTG), which is now the second-leading aetiology of acute pancreatitis in China.MethodsThe patient and his family were assessed for gene variants by Sanger sequencing of exons and exon-intron junctions of the LPL, GPIHBP1, APOA5, APOC2, and LMF1 genes. Post-heparin blood was collected for LPL mass and activity detection.ResultsThe patient had suffered from long-term severe hypertriglyceridemia and recurrent abdominal pain for over 30 years, since age 26, and 3 bouts of acute pancreatitis. Two heterozygous LPL single-nucleotide polymorphisms (SNPs) were compound but dislinked: a single-nucleotide substitution (c.42G > A) resulting in the substitution of tryptophan with a stop codon (p.W14X) in one allele, and a single-nucleotide substitution (c.835C > G) resulting in a leucine-to-valine substitution (p.L279 V) in another allele. Only one SNP, p.L279 V, was detected in his son. Post-heparin LPL activity and mass were also lower in the patient.ConclusionTwo heterozygous LPL SNPs, W14X and L279 V, were newly found to be compound but dislinked, which may cause long-term severe hypertriglyceridemia and recurrent acute pancreatitis.

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“…Cys278-p.Cys283) and (p.Cys264-p.Cys275) 18,19. Multiple-species sequence alignment results showed that p.Leu279 was evolutionarily highly conserved, which indicates the significance of p.Leu279 in both the structure and function of wild-type LPL protein.Here, we also identified a heterozygous missense variant (c.553G>T; p.Gly185Cys) in APOA5 gene in the proband 1 (II-2) and his younger son (III-2).…”

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confidence: 90%

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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Genotype-phenotype studies of six novelLPL mutations in Chinese patients with hypertriglyceridemia

Cited by 18 publications

References 32 publications

Superparamagnetic iron oxide nanoparticles alter expression of obesity and T2D-associated risk genes in human adipocytes

Superparamagnetic iron oxide nanoparticles alter expression of obesity and T2D-associated risk genes in human adipocytes

Compound but non-linked heterozygous p.W14X and p.L279 V LPL gene mutations in a Chinese patient with long-term severe hypertriglyceridemia and recurrent acute pancreatitis

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

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