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Polymorphisms in the APOA1/C3/A4/A5 gene cluster and cholesterol responsiveness to dietary change

  • Jaroslav A. Hubacek , Romana Bohuslavova , Zdena Skodova , Jan Pitha , Dagmar Bobkova and Rudolf Poledne
Published/Copyright: March 22, 2007
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Volume 45 Issue 3

Abstract

Background: The relationship between dietary composition and plasma lipids is to some extent genetically determined. It has been found that variants of some genes (e.g., apolipoprotein E and cholesterol 7-α hydroxylase) play an important role in changes in plasma lipid levels in response to dietary intervention. We analyzed the effect of variation in the apolipoprotein (APO) APOA1/C3/A4/A5 gene cluster on decreases in plasma cholesterol levels over an 8-year follow-up study.

Methods: Men (n=133) from the Czech population, for which dietary composition has markedly changed (red meat 80→68 kg/person/year, animal fat 16→9 kg/person/year, fruits and vegetables 133→150 kg/person/year) were recruited. APOA1 (G–75>A and C83>T), APOC3 (C–482>T and C3238>G), APOA4 (Thr347>Ser and Gln360His) and APOA5 (T–1131>C, Ser19>Trp and Val153>Met) variants were analyzed by PCR and restriction analysis. Lipid levels were analyzed in 1988 and 1996. Dietary information was obtained from the Institute of Agricultural Economy.

Results: In APOA5 Ser19Ser homozygotes (n=105), plasma cholesterol was relatively stable over the years (6.1±1.3 and 5.6±1.0 mmol/L in 1988 and 1996), but the decrease was much higher in Trp19 carriers (n=27; 6.5±1.6 vs. 5.1±1.1 mmol/L). This difference in change is significant at p<0.005. Similarly, a better response to dietary changes was detected in carriers of the common APOA4 haplotypes Thr-347Thr/Gln360Gln and Thr347Ser/Gln360Gln (n=102; 6.3±1.3 and 5.5±1.1 mmol/L in 1988 and 1996, p<0.001). Total cholesterol was relatively stable over time in carriers (n=18) of at least one His360 allele and/or two Ser347 alleles (5.7±1.1 and 5.5±0.9  mmol/L in 1988 and 1996, n.s.). Other variants analyzed did not influence the change in lipid measurements over time.

Conclusions: APOA4 and APOA5 variants may play an important role in the individual sensitivity of lipid parameters to dietary composition in men.

Clin Chem Lab Med 2007;45:316–20.

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Corresponding author: Jaroslav Hubacek, PhD, IKEM-CEM, Laboratory for Molecular Genetics, Videnska 1958/9, 140 21 Prague 4, Czech Republic Phone: +420-261-363367,

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Published Online: 2007-03-22
Published in Print: 2007-03-01

©2007 by Walter de Gruyter Berlin New York

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