title: APOA5 Ala315>Val, identified in patients with severe hypertriglyceridemia, is a common mutation with no major effects on plasma lipid levels.
abstract: BACKGROUND
  The importance of the apolipoprotein A5 (APOA5) gene in determining plasma triglyceride (TG) levels has been demonstrated in transgenic and knockout mice and confirmed by human association studies in different ethnic groups.
  
  
  METHODS
  We screened for nonsynonymous APOA5 mutations in patients with plasma TG levels >10 mmol/L. The coding sequence and promoter region of the APOA5 gene were sequenced in 95 individuals with severe hypertriglyceridemia (HTG). A large population sample of 3,202 individuals was screened by PCR and restriction analysis for presence of detected mutation.
  
  
  RESULTS
  In total, three heterozygous carriers of 944C>T (Ala315>Val) were identified in the severe HTG patients, while 22 carriers were identified in the population sample. The rare allele frequency of the Val315 was significantly higher in the HTG sample than in controls (0.016 vs. 0.003, p<0.01, respectively). Most of the control Ala315Val carriers, however, had plasma lipid levels (TGs, total cholesterol and high-density lipoprotein cholesterol) within the usual range detected in the population.
  
  
  CONCLUSIONS
  APOA5 Ala315>Val does not play any dominant/important role in the genetic determination of plasma TG levels, but the increased frequency in HTG patients compared to controls suggests that it might interact with other gene variants to cause HTG.
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic. jaroslav.hubacek@ikem.cz
authors.forename: Jaroslav A
authors.initials: JA
authors.lastname: Hubacek
authors.forename: Wu-Wei
authors.initials: WW
authors.lastname: Wang
authors.forename: Zdena
authors.initials: Z
authors.lastname: Skodová
authors.forename: Vera
authors.initials: V
authors.lastname: Adámková
authors.forename: Michal
authors.initials: M
authors.lastname: Vráblík
authors.forename: Ales
authors.initials: A
authors.lastname: Horínek
authors.forename: Tomás
authors.initials: T
authors.lastname: Stulc
authors.forename: Richard
authors.initials: R
authors.lastname: Ceska
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
mesh_terms: D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D003604:Czechoslovakia; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014280:Triglycerides / Q000097:blood*
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D014280:Triglycerides; D002784:Cholesterol