title: Impact of apolipoprotein A5 polymorphisms on insulin sensitivity and beta-cell function.
abstract: OBJECTIVE
  Alternation in lipid metabolism can affect both insulin sensitivity and beta-cell function. Apolipoprotein A5 (APOA5) is an important determinant of lipid metabolism. The impact of the APOA5 gene on insulin sensitivity and beta-cell function has not been examined.
  
  
  METHODS
  We examined the influence of 2 amino acid polymorphisms (V150M and G182C) in the APOA5 gene on insulin sensitivity and beta-cell function in 67 glucose-tolerant white subjects. Insulin sensitivity index (ISI) and first- and second-phase insulin responses (1stIR and 2ndIR) were assessed using a hyperglycemic clamp technique.
  
  
  RESULTS
  We identified 59 VV and 8 VM subjects, and none had either the GC or CC genotype. Although no association was found with fasting lipid profile and plasma glucose concentrations during oral glucose tolerance test, the V150M was associated with higher 1stIR (P = 0.0010) and 2ndIR (P = 0.0016) and lower ISI (P = 0.0135). The associations of this polymorphism with 1stIR (P = 0.0081) and 2ndIR (P = 0.0087) were independent of sex, age, and body mass index, but not ISI.
  
  
  CONCLUSIONS
  The V150M polymorphism had an independent influence on 1stIR and 2ndIR. Although the biologic consequence of this polymorphism remains to be determined, the V150M polymorphism in the APOA5 gene is a genetic marker for beta-cell function.
authors.affiliation: Division of Clinical Epidemiology and Preventive Medicine, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. kchiu@mednet.ucla.edu
authors.forename: Ken C
authors.initials: KC
authors.lastname: Chiu
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.forename: Avetis Arthur
authors.initials: AA
authors.lastname: Boyadjian
authors.forename: Sandra
authors.initials: S
authors.lastname: Fernando
authors.forename: Connie
authors.initials: C
authors.lastname: Kwan
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D000328:Adult; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A; D005260:Female; D005838:Genotype; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A