title: ABCC6 gene polymorphism associated with variation in plasma lipoproteins.
abstract: The ATP cassette-binding (ABC) gene superfamily contains more than 40 members, many of which are involved in cellular lipid transport. The most prominent example is ABCA1, mutations in which affect plasma high-density lipoprotein (HDL) cholesterol concentration. ABCC6 is another member of the ABC gene family, and mutations in ABCC6 were recently shown to cause pseudoxanthoma elasticum (PXE). A Canadian patient with PXE was referred for assessment of moderately severe type IV hyperlipoproteinemia with hypoalphalipoproteinemia, which was refractory to pharmacological treatment. We identified intron-exon boundaries of ABCC6 to sequence genomic DNA from this patient to find the disease mutation. We report (1) identification of a set of amplification primers for the 31 exons of ABCC6; (2) identification of the ABCC6 R>X1164 nonsense mutation in the PXE subject with dyslipidemia; (3) identification of common amino acid variants and silent nucleotide variants in ABCC6, with a range of allele frequencies across ethnic groups; (4) evidence consistent with a possible pseudogene encoding 9 exons with sequence homology to ABCC6; and (5) association of the ABCC6 R>Q1268 variant with plasma triglyceride and HDL cholesterol. The results suggest that ABCC6 may be a determinant of plasma lipoproteins.
authors.affiliation: Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Near
authors.forename: K
authors.initials: K
authors.lastname: Young
authors.forename: P W
authors.initials: PW
authors.lastname: Connelly
authors.forename: R A
authors.initials: RA
authors.lastname: Hegele
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D018389:Codon, Nonsense; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000097:blood / Q000150:complications / Q000235:genetics; D007438:Introns; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D011544:Pseudogenes; D011561:Pseudoxanthoma Elasticum / Q000097:blood / Q000150:complications / Q000235:genetics; D019655:Quantitative Trait, Heritable
chemical_list: D018389:Codon, Nonsense; D017931:DNA Primers; D008074:Lipoproteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human