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Titolo:
Structure of the human acyl-CoA : cholesterol acyltransferase-2 (ACAT-2) gene and its relation to dyslipidemia
Autore:
Katsuren, K; Tamura, T; Arashiro, R; Takata, K; Matsuura, T; Niikawa, N; Ohta, T;
Indirizzi:
Univ Ryukyus, Fac Med, Dept Pediat, Nishihara, Okinawa 9030125, Japan UnivRyukyus Nishihara Okinawa Japan 9030125 hara, Okinawa 9030125, Japan Hiroshima Hosp, W Japan Railway Co, Dept Internal Med 2, Hiroshima, Japan Hiroshima Hosp Hiroshima Japan o, Dept Internal Med 2, Hiroshima, Japan Nagasaki Univ, Sch Med, Dept Human Genet, Nagasaki 8528523, Japan NagasakiUniv Nagasaki Japan 8528523 uman Genet, Nagasaki 8528523, Japan
Titolo Testata:
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
fascicolo: 3, volume: 1531, anno: 2001,
pagine: 230 - 240
SICI:
1388-1981(20010430)1531:3<230:SOTHA:>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
COENZYME-A; NONHUMAN-PRIMATES; MOLECULAR-CLONING; TRANSGENIC MICE; MESSENGER-RNA; B SECRETION; HUMAN LIVER; EXPRESSION; LIPOPROTEINS; MACROPHAGES;
Keywords:
acyl coenzyme A : cholesterol acyltransferase-2; lipoprotein; dyslipidemia; cholesterol esterification; apolipoprotein C-III; atherosclerosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Ohta, T Univ Ryukyus, Fac Med, Dept Pediat, 207 Uehara, Nishihara, Okinawa9030125, Japan Univ Ryukyus 207 Uehara Nishihara Okinawa Japan 9030125 125, Japan
Citazione:
K. Katsuren et al., "Structure of the human acyl-CoA : cholesterol acyltransferase-2 (ACAT-2) gene and its relation to dyslipidemia", BBA-MOL C B, 1531(3), 2001, pp. 230-240

Abstract

Acyl-CoA :cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification in mammalian cells. Two isoforms of ACAT have been reported to date(ACAT-I and ACAT-2). ACAT-1 is ubiquitously expressed in tissues except the intestine. In contrast. ACAT-2 is expressed mainly in the intestine in humans. To investigate the relationship between ACAT-2 and dyslipidemia, we determined the structure of the human ACAT-2 gene and then studied the relationship between mutations of the ACAT-2 gene and dyslipidemia. To isolate human ACAT-2 genomic DNA, we designed primers based on the human ACAT-2 cDNAsequence: forward primer 5 ' -ACACCTCGATCTTGGTCCTGCCATA-3 ' and reverse primer 5 ' -GGAATGCAGACAGGGAGTCCT-3 '. Using these primers, a human Pi-derived artificial chromosome (PAC) library was screened by PCR-based procedures. Isolated PAC clones were completely digested with BamHI and subcloned intoplasmid vector. Subclones that contained exons were screened by dot-blot hybridization using partial ACAT-2 cDNA fragments. The coding region of the ACAT-2 gene was encoded in 15 exons from 51 to 265 base pairs on a 21 kilobase span of genomic DNA. The exonic sequences coincided completely with that of ACAT-2 cDNA, and each exon-intron junction conserved splicing consensus sequences. Next, 187 (91 dyslipidemic and 96 normolipidemic) subjects were screened by PCR single-strand conformational polymorphism analysis of theACAT-2 gene. Three mutations were identified by DNA sequencing: two missense mutations (E14G in exon 1 and T254I in exon 7) and a point mutation in intron 7 (-35G -->A). Mutations in exon I and intron 7 were not associated with plasma concentrations of lipids and apolipoproteins (apo). However, plasma apoC-III levels in T254I heterozygotes were significantly higher than those in subjects without mutation. Plasma triglyceride (TG) levels in T254II heterozygotes were similar to those in subjects without mutation. Although further studies are needed, our data suggest that ACAT-2 may contribute to apoC-III gene expression and the assembly of apoC-III and TG, possibly in the intestine. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/02/20 alle ore 02:39:53