ABCMdb

PMID: 15066991

Kockx M, Rye KA, Gaus K, Quinn CM, Wright J, Sloane T, Sviridov D, Fu Y, Sullivan D, Burnett JR, Rust S, Assmann G, Anantharamaiah GM, Palgunachari MN, Katz SL, Phillips MC, Dean RT, Jessup W, Kritharides L
Apolipoprotein A-I-stimulated apolipoprotein E secretion from human macrophages is independent of cholesterol efflux.
J Biol Chem. 2004 Jun 18;279(25):25966-77. Epub 2004 Apr 1., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCA1 p.Ala1046Asp ABCA1 p.Cys733Arg Finally, apoA-I stimulates apoE secretion normally from macrophages of two unrelated subjects with genetically confirmed Tangier Disease (mutations C733R and c.5220-5222delTCT; and mutations A1046D and c.4629-4630insA), despite severely inhibited cholesterol efflux. Login to comment 127 ABCA1 p.Cys733Arg Two novel amino acid mutations within the ABCA1 gene were found: C733R in exon 16 (c.2197CϾT) and a deletion of three nucleotides in exon 38 (c.5220-5222delTCT) on different alleles as shown by segregation analysis (numbering follows recommendations of the international nomenclature working group). Login to comment 128 ABCA1 p.Cys733Arg Two novel amino acid mutations within the ABCA1 gene were found: C733R in exon 16 (c.2197Cb0e;T) and a deletion of three nucleotides in exon 38 (c.5220-5222delTCT) on different alleles as shown by segregation analysis (numbering follows recommendations of the international nomenclature working group). Login to comment 134 ABCA1 p.Ala1046Asp Using current nomenclature, these are respectively equivalent to a missense mutation in exon 22 (c.3137CϾA; A1046D) and a frameshift mutation in exon 34 (c.4629-4630insA; A1544 fs X1552). Login to comment 135 ABCA1 p.Ala1046Asp ABCA1 p.Ala1046Asp HC2 has neither ABCA1 mutation, and HZ2A and HZ2B contain the 4629insA and the A1046D mutations, respectively. Login to comment 136 ABCA1 p.Ala1046Asp HC2 has neither ABCA1 mutation, and HZ2A and HZ2B contain the 4629insA and the A1046D mutations, respectively. Login to comment 309 ABCA1 p.Cys733Arg The first subject with TD (TD1, see "Experimental Procedures"), was a compound heterozygote for the novel ABCA1 mutations C733R in exon 16 and a deletion of three nucleotides (c.5220-5222 delTCT) in exon 38 (TD1-HMDM). Login to comment 310 ABCA1 p.Cys733Arg The first subject with TD (TD1, see "Experimental Procedures"), was a compound heterozygote for the novel ABCA1 mutations C733R in exon 16 and a deletion of three nucleotides (c.5220-5222 delTCT) in exon 38 (TD1-HMDM). Login to comment 320 ABCA1 p.Ala1046Asp ABCA1 p.Ala1046Asp Cells from TD2, who is compound heterozygote for mutations A1046D and c.4629-4630insA, were compared with those of his healthy brother known to be free of ABCA1 mutations (HC2-HMDM), and his heterozygous parents with mutations 4629insA (HZ2A-HMDM) and A1046D (HZ2B-HMDM) (44, 45) (Table III, B). Login to comment 321 ABCA1 p.Ala1046Asp ABCA1 p.Ala1046Asp Cells from TD2, who is compound heterozygote for mutations A1046D and c.4629-4630insA, were compared with those of his healthy brother known to be free of ABCA1 mutations (HC2-HMDM), and his heterozygous parents with mutations 4629insA (HZ2A-HMDM) and A1046D (HZ2B-HMDM) (44, 45) (Table III, B). Login to comment 346 ABCA1 p.Ala1046Asp ABCA1 p.Ala1046Asp ABCA1 p.Cys733Arg Subject Mutation HDL-C Basal apoE secretion ApoA-I-specific cholesterol efflux ApoA-I-stimulated apoE secretion mg/dL òe;g/mg cell protein òe;g/mg cell protein Aa HC1 44.0b 2.2 afe; 0.49b 3.1 afe; 0.5b 6.3 afe; 0.9 TD1 C733R;C.5220-5222delTCT 3.1 0.5 afe; 0.21 0.5 afe; 0.5 5.6 afe; 1.2 Bc HC2 43.0d 1.1 afe; 1.6 2.2 afe; 0.4d 4.2 afe; 1.0 TD2d A1046D;4629insA 2.7 NDe 0.2 afe; 0.2 3.8 afe; 0.7 HZ2A 4629insA 25.8d ND 1.9 afe; 0.3d 2.6 afe; 0.6 HZ2B A1046D 38.6d 1.4 afe; 0.2 2.8 afe; 0.1d 4.5 afe; 0.9 a Part A: macrophages from newly characterized TD1 and unrelated control subject HC1 were compared for cholesterol efflux and apoE secretion in the presence and absence of 25 òe;g/ml apoA-I. Cholesterol efflux and apoE secretion were determined at 8 h, and apoA-I-specific efflux derived by subtracting efflux to control medium (without A-I) from that to apoA-I. b Conditions are significantly different between HC1 and TD1, p b0d; 0.01. c Part B: TD2 has previously been described (44). Login to comment 348 ABCA1 p.Ala1046Asp ABCA1 p.Ala1046Asp ABCA1 p.Cys733Arg Subject Mutation HDL-C Basal apoE secretion ApoA-I-specific cholesterol efflux ApoA-I-stimulated apoE secretion mg/dL ␮g/mg cell protein ␮g/mg cell protein Aa HC1 44.0b 2.2 Ϯ 0.49b 3.1 Ϯ 0.5b 6.3 Ϯ 0.9 TD1 C733R;C.5220-5222delTCT 3.1 0.5 Ϯ 0.21 0.5 Ϯ 0.5 5.6 Ϯ 1.2 Bc HC2 43.0d 1.1 Ϯ 1.6 2.2 Ϯ 0.4d 4.2 Ϯ 1.0 TD2d A1046D;4629insA 2.7 NDe 0.2 Ϯ 0.2 3.8 Ϯ 0.7 HZ2A 4629insA 25.8d ND 1.9 Ϯ 0.3d 2.6 Ϯ 0.6 HZ2B A1046D 38.6d 1.4 Ϯ 0.2 2.8 Ϯ 0.1d 4.5 Ϯ 0.9 a Part A: macrophages from newly characterized TD1 and unrelated control subject HC1 were compared for cholesterol efflux and apoE secretion in the presence and absence of 25 ␮g/ml apoA-I. Cholesterol efflux and apoE secretion were determined at 8 h, and apoA-I-specific efflux derived by subtracting efflux to control medium (without A-I) from that to apoA-I. b Conditions are significantly different between HC1 and TD1, p Ͻ 0.01. c Part B: TD2 has previously been described (44). Login to comment