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Titolo:
Cholesteryl ester transfer protein gene effect on CETP activity and plasmahigh-density lipoprotein in European populations
Autore:
Gudnason, V; Kakko, S; Nicaud, V; Savolainen, MJ; Kesaniemi, YA; Tahvanainen, E; Humphries, S;
Indirizzi:
Univandndon Univ Coll, Sch Med, Rayne Inst, Dept Med, London WC1E 6JJ, Engl Univ London Univ Coll London England WC1E 6JJ Med, London WC1E 6JJ, Engl Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland Univ Oulu Oulu Finland SF-90220 ept Internal Med, SF-90220 Oulu, Finland Univ Oulu, Bioctr, Oulu, Finland Univ Oulu Oulu FinlandUniv Oulu, Bioctr, Oulu, Finland INSERM, U258, Paris, France INSERM Paris FranceINSERM, U258, Paris, France Natl Publ Hlth Inst, Dept Biochem, Helsinki, Finland Natl Publ Hlth Inst Helsinki Finland t, Dept Biochem, Helsinki, Finland
Titolo Testata:
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 2, volume: 29, anno: 1999,
pagine: 116 - 128
SICI:
0014-2972(199902)29:2<116:CETPGE>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIPID-TRANSFER PROTEIN; CORONARY HEART-DISEASE; DIAGONAL GEL-ELECTROPHORESIS; HDL-CHOLESTEROL; APOLIPOPROTEIN-E; MESSENGER-RNA; SUBFRACTION DISTRIBUTION; MYOCARDIAL-INFARCTION; POSTPRANDIAL LIPEMIA; ADIPOSE-TISSUE;
Keywords:
cholesteryl ester transfer protein; coronary artery disease risk; genetic polymorphisms; high-density lipoprotein;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Gudnason, V UnivELondon Univ Coll, Sch Med, Rayne Inst, Dept Med, 5 Univ St, London WC1 Univ London Univ Coll 5 Univ St London England WC1E 6JJ n WC1
Citazione:
V. Gudnason et al., "Cholesteryl ester transfer protein gene effect on CETP activity and plasmahigh-density lipoprotein in European populations", EUR J CL IN, 29(2), 1999, pp. 116-128

Abstract

Background Variation at the cholesteryl ester transfer protein (CETP) genelocus has been implicated in determining the levels and activity of CETP, apoAI and high-density lipoprotein (HDL) plasma concentration and the risk of developing coronary artery disease. Study design The effects of two common polymorphisms of CETP, TaqIB in intron 1 and isoleucine 405 to valine (I405 --> V) in exon 14, were examined in a sample of 822 men age 18-28 years from 11 countries in Europe who had participated in a study (the European Atherosclerosis Research Study II) of the offspring of myocardial infarction sufferers before the age of 55 yearsand age-matched control subjects. Results The frequency of the rare TaqIB allele (B2) and the rare V405 allele was 0.44 and 0.28 respectively and was the same in different regions of Europe. There was a moderate linkage disequilibrium between the two polymorphisms in all the regions (D' = +0.31, P < 0.001), explained by the preferential association between the two common alleles, B1 and I405. There was a statistically significant association of the rare alleles for both the polymorphisms with lower activity of CETP (P < 0.001), 11.2% lower for the TaqIB and 7.0% lower for the I405 --> V polymorphism. The TaqIB polymorphism explained 9.1% (P < 0.001) and I405 --> V explained 3.7% (P < 0.001) of the variance in CETP activity, and in combination these genotypes explained 12.0% of the variance (P < 0.001). Overall, subjects whose fathers had had an early coronary heart disease had 2.4% higher plasma CETP activity than thosewithout such family history, which became statistically significant when adjusted for the effect of the genotypes (P = 0.015), but the significance disappeared after adjustment for the effect of lipids. There was a statistically significant effect of the TaqIB polymorphism on both plasma HDL cholesterol and apoAI level (P < 0.001), with those homozygous for the rare B2 allele having the highest level. Those individuals homozygous for the rare V405 allele had the highest HDL and apoAI levels, although these effects onlyreached statistical significance for HDL (P < 0.03). Conclusion These results suggest that the TaqIB and I405 --> V polymorphisms represent two independent functional variations in the CETP gene that may affect the activity of CETP and thus plasma levels of HDL.

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Documento generato il 16/07/20 alle ore 19:53:38