Molecular variation at the apolipoprotein�B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis

Abstract

Apolipoprotein B (apoB) is the sole protein component of low-density lipoprotein (LDL) and is thought to play an important role in atherogenesis. We performed a meta-analysis of the associations between the three most frequently investigated polymorphisms (XbaI, signal peptide insertion/deletion, EcoRI) in the apolipoprotein B (APOB) gene, lipid parameters, and the risk of ischemic heart disease (IHD). We restricted our analysis to Caucasians. Homozygotes for the XbaI X+ allele had significantly elevated levels of LDL cholesterol (LDL-C) and apoB, but a decreased risk (OR=0.80; 95%CI: 0.66-0.96) of IHD. Homozygosity for the signal peptide deletion allele was associated with similarly increased levels of LDL-C and apoB, and with an increased risk of IHD (OR=1.30; 95%CI: 1.08-1.58). Subjects homozygous for the rare EcoRI allele had significantly decreased levels of total and LDL cholesterol, but unaltered risk of IHD. We conclude that all three polymorphic apoB sites are associated with altered lipid levels, but not necessarily with a consistently altered risk of IHD. These data suggest that the relationship between apoB levels, hypercholesterolemia and IHD risk cannot have a simple molecular basis in the apoB gene.

Apolipoprotein B signal peptide polymorphism and plasma LDL-cholesterol response to low-calorie diet

“…Our results in this population of obese subjects on spontaneous diet show an increase of the concentration of the LDL-cholesterol with the Del allele, which is in good agreement with most of the studies [7][8][9][10][11][12][13][14][15] but not all. [21][22][23] Nevertheless, the discrepancies between studies could be due to a different selection of subjects, in particular concerning the BMI, since in the latter studies, [21][22][23] subjects are described as 'healthy' or 'normal'.…”

“…[7][8][9][10][11][12][13][14] A recent meta-analysis has shown that subjects with the Del/Del apoB genotype had higher cholesterol levels and an increased risk of coronary heart disease. 15 Improvements in the metabolic status of overweight patients can be achieved by even moderate weight loss: in particular, favorable changes in lipid profiles are observed. Genetic factors could also be involved in the variability of these changes.…”

Multiple genetic determinants of plasma lipid levels in Caribbean Hispanics

“…Four SNPs at APOB were significantly related to lipids in our population: promoter SNP rs934197, non-synonymous SNPs rs1367117, rs1042031 and rs1801702. The most significant SNP rs1367117 is 2875 bp away from the extensively studied Ins/Del polymorphism [3]; therefore, it might tag the effect of the functional Ins/Del polymorphism. For SNP rs1042031 (aka EcoRI), the mean differences between the rare and common homozygous genotypes in our study (12.65 mg/dL) were similar to a meta-analysis that included 33 publications (15.46 mg/dL) [3], suggesting that the APOB gene exerted a comparable effect across ethnic groups.…”

“…An SNP with the minor allele frequency (MAF) >0.05 and submitted to the dbSNP database by more than one source were mandatory requirements. Candidate SNPs that are most likely to be biologically relevant were selected using the following criteria: (1) non-synonymous SNPs, (2) had been examined in previous genetic studies, (3) with known functional relevance, or (4) located at evolutionarily conserved sequence homology (Vista website,http://genome.lbl.gov/vista/index.shtml). We also selected tagging SNPs across different human populations from the SeattleSNPs website (http://pga.gs.washington.edu/genes_genotyped.html).…”

“…Approximately half of the variability in plasma lipid levels is determined by genetic factors [1]. Several genes, such as the apolipoprotein A5 (APOA5), apolipoprotein B (APOB), apolipoprotein E (APOE), and cholesterol ester transfer protein (CETP) genes, have been reported to be related to the lipid profiles in whites and blacks [2][3][4][5]. However, only few of them (APOA5, APOE, and CETP) have been investigated in Hispanics [6][7][8].…”