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Titolo:
Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease
Autore:
Clee, SM; Zwinderman, AH; Engert, JC; Zwarts, KY; Molhuizen, HOF; Roomp, K; Jukema, JW; van Wijland, M; van Dam, M; Hudson, TJ; Brooks-Wilson, A; Genest, J; Kastelein, JJ; Hayden, MR;
Indirizzi:
Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada Univ British Columbia Vancouver BC Canada V5Z 4H4 ver, BC V5Z 4H4, Canada Leiden Univ, Med Ctr, Dept Med Stat, Leiden, Netherlands Leiden Univ Leiden Netherlands Ctr, Dept Med Stat, Leiden, Netherlands McGill Univ, Ctr Hlth, Montreal Genome Ctr, Montreal, PQ, Canada McGill Univ Montreal PQ Canada Montreal Genome Ctr, Montreal, PQ, Canada Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands Acad Med Ctr Amsterdam Netherlands ept Vasc Med, Amsterdam, Netherlands Xenon Genet Inc, Vancouver, BC, Canada Xenon Genet Inc Vancouver BC Canada non Genet Inc, Vancouver, BC, Canada Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands Leiden Univ Leiden Netherlands d Ctr, Dept Cardiol, Leiden, Netherlands Interuniv Cardiol Inst, Leiden, Netherlands Interuniv Cardiol Inst Leiden Netherlands iol Inst, Leiden, Netherlands McGill Univ, Ctr Hlth, Cardiovasc Genet Lab, Montreal, PQ, Canada McGill Univ Montreal PQ Canada ardiovasc Genet Lab, Montreal, PQ, Canada
Titolo Testata:
CIRCULATION
fascicolo: 9, volume: 103, anno: 2001,
pagine: 1198 - 1205
SICI:
0009-7322(20010306)103:9<1198:CGVIAI>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
BINDING CASSETTE TRANSPORTER-1; HDL CHOLESTEROL LEVELS; TANGIER-DISEASE; HEART-DISEASE; P-GLYCOPROTEIN; DEFICIENCY; MUTATIONS; EFFLUX; MICE; TRIGLYCERIDE;
Keywords:
ABC transporters; coronary disease; lipids; genetics;
Tipo documento:
Reprint
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Hayden, MR Univ British Columbia, Ctr Mol Med & Therapeut, 980 W 28th Ave,Vancouver,BC V5Z 4H4, Canada Univ British Columbia 980 W 28th Ave Vancouver BC Canada V5Z 4H4
Citazione:
S.M. Clee et al., "Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease", CIRCULATION, 103(9), 2001, pp. 1198-1205

Abstract

Background-Low plasma HDL cholesterol (HDL-C) is associated with an increased risk of coronary artery disease (CAD). We recently identified the ATP-binding cassette transporter 1 (ABCA1) as the major gene underlying the HDL deficiency associated with reduced cholesterol efflux, Mutations within theABCA1 gene are associated with decreased HDL-C, increased triglycerides, and an increased risk of CAD. However, the extent to which common variation within this gene influences plasma lipid levels and CAD in the general population is unknown. Methods and Results-We examined the phenotypic effects of single nucleotide polymorphisms in the coding region of ABCA1, The R219K variant has a carrier frequency of 46% in Europeans. Carriers have a reduced severity of CAD,decreased focal (minimum obstruction diameter 1.8 1 +/- 0.35 versus 1.73 +/- 0.35 mm in noncarriers, P=0.001) and diffuse atherosclerosis (mean segment diameter 2.77 +/- 0.37 versus 2.70 +/- 0.37 mm, P=0.005), and fewer coronary events (50% versus 59%, P=0.02). Atherosclerosis progresses more slowly in carriers of R219K than in noncarriers, Carriers have decreased triglyceride levels (1.42 +/- 0.49 versus 1.84 +/- 0.77 mmol/L, P=0.001) and a trend toward increased HDL-C (0.91+/- 0.22 versus 0.88 +/- 0.20 mmol/L, P=0.12). Other single nucleotide polymorphisms in the coding region had milder effects on plasma lipids and atherosclerosis. Conclusions-These data suggest that common variation in ABCA1 significantly influences plasma lipid levels and the severity of CAD.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 08:29:50