title: Haplotype analyses of the APOA5 gene in patients with familial combined hyperlipidemia.
abstract: BACKGROUND
  Familial combined hyperlipidemia (FCH) is the most common genetic lipid disorder with an undefined genetic etiology. Apolipoprotein A5 gene (APOA5) variants were previously shown to contribute to FCH. The aim of the present study was to evaluate the association of APOA5 variants with FCH and its related phenotypes in Dutch FCH patients. Furthermore, the effects of variants in the APOA5 gene on carotid intima-media thickness (IMT) and cardiovascular disease (CVD) were examined.
  
  
  METHODS
  The study population consisted of 36 Dutch families, including 157 FCH patients. Two polymorphisms in the APOA5 gene (-1131T>C and S19W) were genotyped.
  
  
  RESULTS
  Haplotype analysis of APOA5 showed an association with FCH (p=0.029), total cholesterol (p=0.031), triglycerides (p<0.001), apolipoprotein B (p=0.011), HDL-cholesterol (p=0.013), small dense LDL (p=0.010) and remnant-like particle cholesterol (p=0.001). Compared to S19 homozygotes, 19W carriers had an increased risk of FCH (OR=1.6 [1.0-2.6]; p=0.026) and a more atherogenic lipid profile, reflected by higher triglyceride (+22%) and apolipoprotein B levels (+5%), decreased HDL-cholesterol levels (-7%) and an increased prevalence of small dense LDL (16% vs. 26%). In carriers of the -1131C allele, small dense LDL was more prevalent than in -1131T homozygotes (29% vs. 16%). No association of the APOA5 gene with IMT and CVD was evident.
  
  
  CONCLUSIONS
  In Dutch FCH families, variants in the APOA5 gene are associated with FCH and an atherogenic lipid profile.
authors.affiliation: Department of Medicine, Division of General Internal Medicine, 463, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Gerly M
authors.initials: GM
authors.lastname: van der Vleuten
authors.forename: Aaron
authors.initials: A
authors.lastname: Isaacs
authors.forename: Wu-Wei
authors.initials: WW
authors.lastname: Zeng
authors.forename: Ewoud
authors.initials: E
authors.lastname: ter Avest
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
mesh_terms: D000328:Adult; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides