Polymorphisms in the APOA1/C3/A4/A5 gene cluster and cholesterol responsiveness to dietary change1)

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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 Gln 360 His) and APOA5(T-1131 > C, Ser 19>Trp and Val 153>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 Ser 19 Ser 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 Trp 19 carriers (n s 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-34 hr/Gln36 In and Thr34 er/Gln36 In (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 Ser 347 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.

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