title: [Mutation-function analysis in the lipoprotein lipase gene of Chinese patients with hypertriglyceridemic type 2 diabetes].
abstract: OBJECTIVE
  To investigate the role of lipoprotein lipase (LPL) gene on Chinese patients with hypertriglyceridemic type 2 diabetes.
  
  
  METHODS
  Three subject groups, including hypertriglyceridemic group, normalipidemic type 2 diabetes group and healthy controls, were recruited and screened for sequence changes in LPL gene with PCR, SSCP, restriction analysis and direct DNA sequencing. LPL mass and activity in post-heparin plasma and in in vitro expression were investigated. Comparative modeling was performed via Swiss-PDB Viewer to provide the potential 2-D structures of wildtype and mutant proteins.
  
  
  RESULTS
  Four missense mutations, Ala71Thr, Val18Ile, Gly188Glu and Glu242Lys, were identified in patients with hypertriglyceridemic type 2 diabetes, and not in both normalipidemic diabetes and the control subjects. The four missense mutations were located in the highly conserved amino acid sites, which are involved in highly conserved exon 3, 5, or 6 regions. They led to reduced LPL mass and enzyme activities in both post-heparin plasma and in vitro expression. The modeled structures displayed the differences to a great extent between the mutant and wide-type molecules.
  
  
  CONCLUSIONS
  These results indicated that the 4 missense mutations lead to LPL deficiency and subsequent hypertriglyceridemia. The LPL deficiency predispose a progressive diabetic pathway to those affected individuals. LPL gene is one of susceptibility gene for hypertriglyceridemic type 2 diabetes.
authors.affiliation: Department of Chemical Pathology, Chinese University of Hong Kong, Hong Kong, China. yangtao2k@hotmail.com
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Ching-wan
authors.initials: CW
authors.lastname: Lam
authors.forename: Man-wo
authors.initials: MW
authors.lastname: Tsang
authors.forename: Lisa Y S
authors.initials: LY
authors.lastname: Chan
authors.forename: Priscilla M K
authors.initials: PM
authors.lastname: Poon
authors.forename: Shang-zhi
authors.initials: SZ
authors.lastname: Huang
authors.forename: Chi-pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D044466:Asian People; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D008071:Lipoprotein Lipase