Apolipoprotein A4-1/2 polymorphism and response of serum lipids to dietarycholesterol in humans

The response of serum lipids to dietary changes is to some extent an innate characteristic, One candidate genetic factor that may affect the response of serum lipids to a change in cholesterol intake is variation in the apoli poprotein A4 gene, known as the APOA4-1/2 or apoA-IVGln360His polymorphism, However, previous studies showed inconsistent results. We therefore fed 10 men and 23 women with the APOA4-1/1 genotype and 4 men and 13 women with t he APOA4-1/2 or -2/2 genotype (carriers of the APOA4-2 allele) two diets hi gh in saturated fat, one containing cholesterol at 12.4 mg/MJ, 136.4 mg/day , and one containing cholesterol at 86.2 mg/MJ, 948.2 mg/day, Each diet was supplied for 29 days in crossover design, The mean response of serum low d ensity lipoprotein cholesterol was 0.44 mmol/l (17 mg/dl) in both subjects with the APOA4-1/1 genotype and in subjects with the APOA4-2 allele [95% co nfidence interval of difference in response, -0.20 to 0.19 mmol/l (-8 to 7 mg/dl)]. The mean response of high density lipoprotein cholesterol was also similar, 0.10 mmol/l (4 mg/dl), in the two APOA-4 genotype groups [95% con fidence interval of difference in response, -0.07 to 0.08 mmol/l (-3 to 3 m g/dl)], Thus, the APOA4-1/2 polymorphism did not affect the response of ser um lipids to a change in the intake of cholesterol in this group of healthy Dutch subjects who consumed a background diet high in saturated fat. Knowl edge of the APOA4-1/2 polymorphism is probably not a generally applicable t ool for the identification of subjects who respond to a change in cholester ol intake.