1. Polymorphisms in the APOA1/C3/A4/A5 gene cluster and cholesterol responsiveness to dietary change.
- Author
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Hubacek, Jaroslav A., Bohuslavova, Romana, Skodova, Zdena, Pitha, Jan, Bobkova, Dagmar, and Poledne, Rudolf
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GENETIC polymorphisms , *CHOLESTEROL , *DIET , *BLOOD lipids , *APOLIPOPROTEIN E , *POLYMERASE chain reaction - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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