title: Analysis of apolipoprotein A-I, lecithin:cholesterol acyltransferase and glucocerebrosidase genes in hypoalphalipoproteinemia.
abstract: Hypoalphalipoproteinemia (HALP) is a dyslipidemia characterized by low HDL-cholesterol (HDL-C) levels with important genetic contribution. However, no common genetic mutations have been found to be associated with this disorder. We screened the promoter and coding sequence of apolipoprotein (apo) A-I and lecithin:cholesterol acyltransferase (LCAT) genes and the 5' apo C-III region by SSCP and heteroduplex analysis, and DNA sequencing in 66 unrelated subjects with recurrent low HDL-C levels. We also analyzed the N370S and L444P variants, in the glucocerebrosidase (GBA) gene by restriction fragment analysis. Three mutations in the apo A-I gene (L144R, W108R, g.1833C>T) and 3 mutations in the LCAT gene (S208T, I178T, IVS3-23C>A) were detected, in six heterozygous subjects. In addition, a novel polymorphic site in LCAT gene (g.4886C>T) has been identified. Allelic frequencies of polymorphisms g.(-636)C>A, g.(-625)G>A, g.(-620)T>del, g.(-479C>T and g.(-452)T>C, located upstream of the apo C-III gene, were in normal range, and no other mutation was found in this region. Two HALP subjects were found to carry the N370S mutation at GBA locus. In conclusion, 12% of HALP subjects were found to carry mutations in apo A-I, LCAT, or GBA genes, which could explain this phenotype. Our results confirm the molecular, genetic and phenotypic heterogeneity of HALP.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: Recalde
authors.forename: Ana
authors.initials: A
authors.lastname: Cenarro
authors.forename: Angel-Luis
authors.initials: AL
authors.lastname: García-Otín
authors.forename: Diego
authors.initials: D
authors.lastname: Gómez-Coronado
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.forename: Miguel
authors.initials: M
authors.lastname: Pocoví
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016632:Apolipoprotein A-I / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D020022:Genetic Predisposition to Disease; D005962:Glucosylceramidase / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007009:Hypolipoproteinemias / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000032:analysis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011446:Prospective Studies; D012680:Sensitivity and Specificity
chemical_list: D016632:Apolipoprotein A-I; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D005962:Glucosylceramidase