THE APO-B-100 GENE ECORI POLYMORPHISM INFLUENCES THE RELATIONSHIP BETWEEN FEATURES OF THE INSULIN-RESISTANCE SYNDROME AND THE HYPER-APO-B AND DENSE LDL PHENOTYPE IN MEN

The aim of this study was to investigate whether the EcoRI polymorphis m of the apolipoprotein B (apoB) gene influences the relationships bet ween features of the insulin resistance syndrome and the dense LDL phe notype and apoB concentrations. A sample of 65 men was divided into tw o groups on the basis of the EcoRI genotype. Forty-four subjects were (+/+) homozygotes for the presence of the EcoRI restriction site that is associated with a glutamic acid at codon 4154. Twenty-one men were (+/-) heterozygotes for the absence of the restriction site resulting from a glutamic acid to a lysine substitution at codon 4154. In the (/-) group, fasting plasma FFA levels were positively correlated with p lasma apoB, LDL-apoB, and the LDL particle score that was calculated f rom the migration distances of LDL subspecies and their relative band intensities, reflecting the proportion of small dense LDL particles. H owever, these associations mere not found among (+/+) subjects. The tw o genotypic groups were further divided into two subgroups on the basi s of fasting FFA concentrations, and the LDL particle score and the LD L-apoB levels were compared. High FFA levels were associated with a hi gher proportion of small dense LDL particles, as reflected by a higher mean LDL particle score, irrespective of the genotype. However, the a poB-EcoRI polymorphism appeared to influence the association between h igh FFA levels and LDL-apoB concentrations because (+/-) heterozygotes with high FFA levels had higher LDL-apoB concentrations than (+/-) he terozygotes with low FFA levels, In addition, the integrated area unde r the curve of plasma insulin concentrations, measured in response to a 75-g oral glucose challenge, and the amount of visceral adipose tiss ue, measured by computed tomography, were positively associated with t he LDL particle score only in (+/-) heterozygotes. When subjects were divided on the basis of insulin area (low VS. high) or visceral adipos e tissue (low vs. high), (+/-) heterozygotes with high insulin area or with high levels of visceral adipose tissue had a higher mean LDL par ticle score than (+/-) heterozygotes with low insulin area or low visc eral adipose tissue. However, among (+/+) homozygotes, low or high lev els of insulin or visceral adipose tissue could not discriminate betwe en men with large or small LDL particles. Therefore, (+/-) heterozygot es may be more susceptible to develop the dense LDL phenotype in prese nce of hyperinsulinemia and visceral obesity. Results of the present s tudy suggest that the apoB-EcoRI polymorphism may exacerbate the alter ations in the LDL particle (size and concentration) found among viscer al obese-hyperinsulinemic men.