Apo B is the exclusive
protein constituent of
LDL and is
ligand on
LDL, recognized and bound by the
LDL receptor. Several restriction fragment length polymorphisms (RFLPs) of the
apo B gene have been shown to be associated with variation in serum
lipid levels in different populations. In this study we sought to determine the frequency of XbaI, EcoRI, and MspI polymorphisms and the haplotypes generated by these three polymorphic sites of the
apo B gene and their influence on
lipid levels in a sample of Norwegian subjects at risk of
atherosclerosis and healthy control subjects.
METHODS AND RESULTS: 108 White Norwegians at risk of
atherosclerosis (cases) and 64 healthy individuals (controls) were examined for possible association between the alleles at the XbaI (X), EcoRI (R), and MspI (M) polymorphic restriction sites of the
apolipoprotein B gene and serum
lipid levels. The frequency of the M allele (absence of restriction site) was significantly higher in cases with high total
cholesterol (TC), high
low-density lipoprotein cholesterol (LDLC), and high
apolipoprotein B (
apo B) than in controls with normal TC, LDLC, and
apo B (P < 0.04, P < 0.02, and P < 0.01, respectively). The frequencies of
apo B genotypes detected with XbaI, EcoRI, and MspI did not differ significantly between cases and control subjects. A significant association between MspI genotypes and TC (P < 0.02), LDLC (P = 0.03), and
apo B (P = 0.001) was observed only in cases. However, cases with the genotype M+/M+ had the lowest and those with the genotype M+/M- had the highest levels of serum TC, LDLC, and
apo B. We did not observe any significant association between the alleles or genotypes detected with XbaI or EcoRI and serum
lipid levels. In cases, genotypes defined by EcoRI and MspI RFLP paired loci differed significantly for
apo B (chi 2 = 19; P = 0.007) but not for other blood
lipids. EcoRI and MspI RFLPs change
glutamic acid (Glu) 4154 to
lysine (Lys) and
arginine (Arg) 3611 to
glutamine (Gln), respectively, which lie near the
low density lipoprotein receptor binding region of
apo B. Haplotypes containing "Lys/
Arg Lys/Arg" (all
basic amino acids) in cases were associated with low serum TC, LDLC, and
apo B. In individuals at risk of
atherosclerosis the concentration of serum
lipids tends to be inversely related to the number of
lysine and
arginine.
CONCLUSION: We conclude that variations in the
apo B gene, resulting in changes of charged
amino acids, affect the circulating blood
lipids and that these may contribute to the risk of
atherosclerosis.