Polymorphisms in the APOA1/C3/A4/A5 gene cluster and cholesterol responsiveness to dietary change.
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-alpha 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.
Hubacek
Jaroslav A
JA
Institute for Clinical and Experimental Medicine, Prague, Czech Republic and Cardiovascular Research Center, Prague, Czech Republic. jahb@medicon.cz
Bohuslavova
Romana
R
Skodova
Zdena
Z
Pitha
Jan
J
Bobkova
Dagmar
D
Poledne
Rudolf
R
D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000235:genetics*; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004032:Diet; D005500:Follow-Up Studies; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D011110:Polymorphism, Genetic
C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; C022205:apolipoprotein A-IV; D004247:DNA; D002784:Cholesterol