Attenuated Hypercholesterolemic Response to a High-Cholesterol Diet in Subjects Heterozygous for the Apolipoprotein A-IV-2 Allele

Abstract

The apo A-IV-2 allele attenuates the hypercholesterolemic response to the short-term ingestion of a very-high-cholesterol diet and may partially account for the heterogeneous response to dietary cholesterol. However, cholesterol intake in this study was more than twice that of the general population; whether the apo A-IV-2 allele alters responsiveness at lower levels of cholesterol intake remains to be determined.

Genetic Variation at the ApoA-IV Gene Locus and Response to Diet in Familial Hypercholesterolemia

“…We did not find differences in baseline lipid levels between carriers of the APOA4-2 allele and carriers of APOA4-1/1, a finding also reported by McCombs et al 17 in normolipidemic subjects. On the other hand, baseline plasma apoB concentrations were significantly lower in our APOA4-2 subjects.…”

“…This hypolipidemic response was similar to what has been described for LDL-C when non-FH individuals consume a low-fat diet. 16,17 Surprisingly, these effects observed for apoB were not paralleled by those observed for LDL-C, for which no allelic differences in dietary response could be demonstrated. These data suggest that dietary intervention may induce remodeling of the LDL particles in Data are meanϮ SD.…”

“…26 ApoA-I, apoB, and apoE are among the genetic loci that have been implicated in the variable lipidic response to dietary changes. Previous studies with apoA-IV conducted in healthy, young normolipidemic individuals 17 and in a multicenter study including volunteers from the general population 16 have shown that individuals carrying the APOA4-360-2 allele have an attenuated hypercholesterolemic response to the ingestion of a very-high-cholesterol diet and decreased LDL-C lowering in response to reductions in dietary saturated fat and cholesterol, respectively. Conversely, in a population study in Costa Rica, 38 it was observed that urban carriers of the APOA4-2 allele had significantly lower HDL-C and apoA-I concentrations and a higher LDL-C/HDL-C ratio than rural APOA4-2 carriers or urban APOA4-1/1 carriers.…”

“…14,15 In dietary intervention trials, carriers of this allele have been shown to be less responsive to dietary changes, in terms of LDL cholesterol (LDL-C), than carriers of the APOA4-1/1 (Gln/Gln) alleles. 16,17 More recently, the APOA4-2 allele was associated with Alzheimer's disease. 18 The application of DNA sequence analysis has revealed additional variation at this locus.…”

Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats

“…In addition, none of the previous studies controlled for known variations in cholesterol absorption associated with apo E or apo A-IV genotypes and all had less stringent dietary control than in this investigation. 16,44,45 Although a recent study showed no difference between different apo E alleles on cholesterol absorption and metabolism, 46 this observation awaits further confirmation because previous studies demonstrated apo E genotype-related differences in cholesterol absorption. 44,45,47,48 In summary, in a healthy population with apo A-IV 1/1 and apo E 3/3 genotypes, supplementation with CDCA or DCA enriched bile with the corresponding bile acid.…”