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Article: Pathogenic mutations of the lipoprotein lipase gene in Chinese patients with hypertriglyceridemic type 2 diabetes.

TitlePathogenic mutations of the lipoprotein lipase gene in Chinese patients with hypertriglyceridemic type 2 diabetes.
Authors
Issue Date2003
Citation
Human Mutation, 2003, v. 21 n. 4, p. 453 How to Cite?
AbstractElevated plasma triglyceride and nonesterified fatty acid concentrations may cause insulin resistance. Lipoprotein lipase (LPL) is a rate-determining enzyme in lipid metabolism. To investigate the role of the LPL gene in Chinese patients with hypertriglyceridemic type 2 diabetes, 277 patients with type 2 diabetes and 241 healthy control subjects were recruited and screened for sequence changes in the LPL gene by PCR, SSCP, restriction analysis and direct DNA sequencing. Ten mutations were identified: four missense mutations, Ala71Thr, Val181Ile, Gly188Glu and Glu242Lys; one nonsense mutation Ser447Ter; and five silent mutations. Ser447Ter was found in both patients and controls with no significant difference in frequency. The four missense mutations were located in the highly conserved exon 3, 5, and 6 regions and in highly conserved amino acid sites. They led to reduced LPL mass and enzyme activities in both post-heparin plasma and in vitro expression. The modeled structures displayed major differences between the mutant and wildtype molecules. These results indicated that the four missense mutations lead to LPL deficiency and subsequent hypertriglyceridemia. Based on our study and published data, a putative pathogenic pathway was suggested: LPL enzyme deficiency causes elevated plasma triglyceride level and subsequent insulin resistance; both increased free fatty acids and insulin resistance promote gluconeogenesis and hyperglycaemia, a vicious circle leading to type 2 diabetes. Copyright 2003 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/148327
ISSN
2023 Impact Factor: 3.3
2023 SCImago Journal Rankings: 1.686
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYang, Ten_US
dc.contributor.authorPang, CPen_US
dc.contributor.authorTsang, MWen_US
dc.contributor.authorLam, CWen_US
dc.contributor.authorPoon, PMen_US
dc.contributor.authorChan, LYen_US
dc.contributor.authorWu, XQen_US
dc.contributor.authorTomlinson, Ben_US
dc.contributor.authorBaum, Len_US
dc.date.accessioned2012-05-29T06:12:15Z-
dc.date.available2012-05-29T06:12:15Z-
dc.date.issued2003en_US
dc.identifier.citationHuman Mutation, 2003, v. 21 n. 4, p. 453en_US
dc.identifier.issn1098-1004en_US
dc.identifier.urihttp://hdl.handle.net/10722/148327-
dc.description.abstractElevated plasma triglyceride and nonesterified fatty acid concentrations may cause insulin resistance. Lipoprotein lipase (LPL) is a rate-determining enzyme in lipid metabolism. To investigate the role of the LPL gene in Chinese patients with hypertriglyceridemic type 2 diabetes, 277 patients with type 2 diabetes and 241 healthy control subjects were recruited and screened for sequence changes in the LPL gene by PCR, SSCP, restriction analysis and direct DNA sequencing. Ten mutations were identified: four missense mutations, Ala71Thr, Val181Ile, Gly188Glu and Glu242Lys; one nonsense mutation Ser447Ter; and five silent mutations. Ser447Ter was found in both patients and controls with no significant difference in frequency. The four missense mutations were located in the highly conserved exon 3, 5, and 6 regions and in highly conserved amino acid sites. They led to reduced LPL mass and enzyme activities in both post-heparin plasma and in vitro expression. The modeled structures displayed major differences between the mutant and wildtype molecules. These results indicated that the four missense mutations lead to LPL deficiency and subsequent hypertriglyceridemia. Based on our study and published data, a putative pathogenic pathway was suggested: LPL enzyme deficiency causes elevated plasma triglyceride level and subsequent insulin resistance; both increased free fatty acids and insulin resistance promote gluconeogenesis and hyperglycaemia, a vicious circle leading to type 2 diabetes. Copyright 2003 Wiley-Liss, Inc.en_US
dc.languageengen_US
dc.relation.ispartofHuman mutationen_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAnimalsen_US
dc.subject.meshCos Cells - Chemistry - Metabolismen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCercopithecus Aethiopsen_US
dc.subject.meshChinaen_US
dc.subject.meshDatabases, Proteinen_US
dc.subject.meshDiabetes Mellitus, Type 2 - Blood - Complications - Enzymology - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshHyperlipoproteinemia Type I - Blood - Enzymology - Geneticsen_US
dc.subject.meshHypertriglyceridemia - Blood - Complications - Enzymology - Geneticsen_US
dc.subject.meshLipoprotein Lipase - Biosynthesis - Blood - Chemistry - Geneticsen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMolecular Weighten_US
dc.subject.meshMutation - Geneticsen_US
dc.subject.meshNuclear Familyen_US
dc.titlePathogenic mutations of the lipoprotein lipase gene in Chinese patients with hypertriglyceridemic type 2 diabetes.en_US
dc.typeArticleen_US
dc.identifier.emailLam, CW:ching-wanlam@pathology.hku.hken_US
dc.identifier.authorityLam, CW=rp00260en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid12655575-
dc.identifier.scopuseid_2-s2.0-0037387858en_US
dc.identifier.volume21en_US
dc.identifier.issue4en_US
dc.identifier.spage453en_US
dc.identifier.isiWOS:000457435600023-
dc.identifier.issnl1059-7794-

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