title: The role of a triplet repeat sequence of the very low density lipoprotein receptor gene in plasma lipid and lipoprotein level variability in humans.
abstract: The biological role of the very low density lipoprotein receptor (VLDL-R) in humans is not yet elucidated. This cellular receptor binds apolipoprotein E (apoE)-containing lipoparticles and is mainly expressed in peripheral tissues. The VLDL-R gene contains a polymorphic triplet (CGG) repeat located 19 bp upstream of the initiation codon. We explored the allelic distribution of this repeat in 1384 subjects of European Caucasian origin, 609 of them surviving a myocardial infarction. Six alleles corresponding to 5, 6, 7, 8, 9, and 11 repeats were detected in this population. The alleles 5, 8, and 9 were the most frequent, with frequencies of 0.413, 0.275, and 0.292, respectively. No association was found between the VLDL-R polymorphism and myocardial infarction. In controls without lipid lowering treatment, a statistically significant interaction between VLDL-R genotype and apoE phenotype was found for plasma triglycerides (P < .04), suggesting a gene-gene interaction. There was also a main effect of the VLDL-R polymorphism on LpE:B and LpA-I. The VLDL-R 9 allele was associated with lower levels of plasma LpE:B (P < .05) and higher concentrations of plasma LpA-I (P < .01) than the other alleles. These results suggest that VLDL-R has a modest influence on circulating lipoproteins in humans.
authors.affiliation: Service d'Epidémiologie et de Santé Publique-INSERM CJF 95-05, Institut Pasteur de Lille, France.
authors.forename: N
authors.initials: N
authors.lastname: Helbecque
authors.forename: J
authors.initials: J
authors.lastname: Dallongeville
authors.forename: V
authors.initials: V
authors.lastname: Codron
authors.forename: D
authors.initials: D
authors.lastname: Arveiler
authors.forename: J B
authors.initials: JB
authors.lastname: Ruidavets
authors.forename: A
authors.initials: A
authors.lastname: Evans
authors.forename: F
authors.initials: F
authors.lastname: Cambien
authors.forename: J C
authors.initials: JC
authors.lastname: Fruchart
authors.forename: P
authors.initials: P
authors.lastname: Amouyel
mesh_terms: D000328:Adult; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D015897:Comorbidity; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics*; D012189:Retrospective Studies; D017741:Survivors; D018911:Trinucleotide Repeats; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL; C036053:VLDL receptor