title: Case report: A novel apolipoprotein A-I missense mutation apoA-I (Arg149Ser)Boston associated with decreased lecithin-cholesterol acyltransferase activation and cellular cholesterol efflux.
abstract: We report a novel heterozygous apolipoprotein A-I (apoA-I) missense mutation (c.517C>A, p.Arg149Ser, designated as apoA-IBoston) in a 67-year-old woman and her 2 sons, who had mean serum high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-I in very large α-1 HDL that were 10%, 35%, and 16% of normal, respectively (all P < .05). The percentage of HDL cholesterol in the esterified form was also significantly (P < .05) reduced to 52% of control values. Cholesteryl ester tranfer protein (CETP) activity was normal. The mean global, adenosine triphosphate (ATP)-binding cassette transporter A1 and scavenger receptor B type I-mediated cellular cholesterol efflux capacity in apoB-depleted serum from affected family members were 41%, 37%, 47%, 54%, and 48% of control values, respectively (all P < .05). lecithin-cholesterol acyltransferase (LCAT) activity in plasma was 71% of controls, whereas in the cell-based assay, it was 73% of control values (P < .05). The data indicate that this novel apoA-I missense is associated with markedly decreased levels of HDL cholesterol and very large α-1 HDL, as well as decreased serum cellular cholesterol efflux and LCAT activity, but not with premature coronary heart disease, similar to other apoA-I mutations that have been associated with decreased LCAT activity.
authors.affiliation: Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
authors.forename: Pimjai
authors.initials: P
authors.lastname: Anthanont
authors.affiliation: Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Boston Heart Diagnostics, Framingham, MA, USA; Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Bela F
authors.initials: BF
authors.lastname: Asztalos
authors.affiliation: Boston Heart Diagnostics, Framingham, MA, USA.
authors.forename: Eliana
authors.initials: E
authors.lastname: Polisecki
authors.affiliation: Steward Health Good Samaritan Cardiology Group, Brockton, MA, USA.
authors.forename: Benoy
authors.initials: B
authors.lastname: Zachariah
authors.affiliation: Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Boston Heart Diagnostics, Framingham, MA, USA; Tufts University School of Medicine, Boston, MA, USA. Electronic address: Ernst.Schaefer@tufts.edu.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: Apolipoprotein A-I; CETP activity; Cellular cholesterol efflux; Genetic mutation; HDL deficiency; LCAT activity