Cholesterol and saturated fat intake determine the effect of polymorphisms at ABCG5/ABCG8 genes on lipid levels in children

Abstract

Purpose: Analysis of mutations in genes of the cholesterol metabolic pathway has not completely explained the interindividual variability of blood cholesterol concentrations attributed to gene-nutrient interactions. Thus, we analyzed polymorphisms in the ABCG5 and ABCG8 genes, involved in the regulation of intestinal cholesterol absorption, with special interest in a potential interaction with diet to determine lipid levels. Methods: The polymorphisms ABCG5 C1950G (Gln604Glu) and ABCG8 C1895T (Ala640Val) were determined by polymerase chain reaction and restriction analysis in 1227 healthy school children, aged 6 to 8 years. Results: No significant differences were found in blood lipid levels between subjects with different genotypes of the two analyzed polymorphisms. However, important differences appeared when separating subjects by their different lipid intake.The presence of the ABCG8 C1895T and ABCG5 C1950G polymorphisms was associated with different plasma total cholesterol, low-density lipoprotein cholesterol complex, and apolipoprotein B levels only in low-cholesterol consumers (significantly for the C1895T polymorphism), and among children within the lower tertile of saturated fat intake (significantly for the C1950G polymorphism). Conclusion: Polymorphisms at the half-transporter ABCG5 and ABCG8 genes affect blood cholesterol concentrations in prepubertal children by influencing dietary responsiveness. This highly significant gene-nutrient interaction could explain the great individual differences in the plasma lipid response to cholesterol and fat intake. Genet Med 2006:8(9):594-599.Atherosclerosis is a complex, multifactorial disease in which many genes, environmental factors, and interactions between them are involved. Increased consumption of cholesterol and saturated fat has been shown to be associated with higher plasma cholesterol levels and increased risk of cardiovascular disease. 1,2 However, well-controlled experimental studies have demonstrated that individuals differ widely in the response of their plasma cholesterol concentrations to dietary cholesterol and saturated fat. 3,4 A genetic determination of this variability has been documented; 5,6 however, the analysis of the influence of common mutations in relevant genes of cholesterol metabolic pathways (apolipoproteins [apo], receptors, and enzymes) on the responsiveness to dietary fat and cholesterol has not completely explained the wide interindividual variability in the responsiveness to diet, 7 suggesting the intervention of other unknown genes and factors. Studies undertaken to determine the relationship between dietary cholesterol absorption and plasma lipoprotein levels showed large individual differences in dietary cholesterol absorption, suggesting a genetic variation among humans in the regulation of this process. 8,9 When cholesterol absorption was studied, two members of the human adenosine triphosphate (ATP) Binding Cassette (ABC) transporter family, 10 ABCG5 and ABCG8, seem to play a capital role. 10,11 These two ATP-dependen...

Single nucleotide polymorphisms in ABCG5 and ABCG8 genes in Chilean subjects with polygenic hypercholesterolemia and controls

“…Similarly, in a previous study by Viturro et al (22), no significant differences were found in blood lipid levels between subjects with different genotypes for the ABCG5 1950C)G and ABCG8 1985C)T polymorphisms. However, when we compared the serum lipid levels according to different genotypes for this genetic variation, no significant differences were observed.…”

ATP-Binding Cassette Transporter G5 and G8 Polymorphisms and Several Environmental Factors with Serum Lipid Levels

“…Hypercholesterolemic subjects carrying the GG genotype of the ABCG8 251A>G SNP also exhibited higher values of HDL-C when compared to other genotypes [54]. However, these associations were not observed in some earlier studies conducted in Caucasian populations with relatively large sample size [31], [36], [37] and also in recent GWA studies [11], [15]. Therefore, this issue needs further exploration.…”

“…Herron et al [30] found that a shift from a low to a high-dietary-cholesterol diet in individuals with the ABCG5 Q604E mutant allele was associated with a greater increase in plasma LDL-C compared to subjects who were heterozygous or who carried only the wild-type allele. Viturro et al [31] showed that heterozygote boys had higher plasma TC, LDL-C and ApoB levels compared to homozygotes of widetype allele, but only in those within the lowest tertile of saturated fat intake. In contrast, Acalovschi et al [32] observed the opposite effect.…”

“…Regarding ABCG8 A632V, Berge et al [34] observed that the V allele was associated with a high plasma TC. In 380 Spanish children, Viturro et al [31] found that the heterozygotes had higher plasma TC and ApoB levels than AA homozygotes, but only in the group with low cholesterol intake. No association of A632V and TC levels was observed in other studies [32], [33], [37].…”

Effect of Five Single Nucleotide Polymorphisms of ABCG5 and ABCG8 Genes on Ezetimibe Lipid-Lowering Response

“…In Mexican hypercholesterolemic subjects, this polymorphism was not significantly associated with reduction in plasma lipids (Torres et al). Interestingly, Viturro et al (2006) found no association among this genetic variant and lipids levels. Nevertheless, when the subjects were separated by lipid intake, the variant rs6720173 C/G of ABCG5 gene was associated with plasma total cholesterol, LDL-C and apolipoprotein B levels.…”