Apolipoprotein B gene polymorphisms and serum lipids: Meta-analysis of the role of genetic variation in responsiveness to diet

Background: The genetic variance determining plasma lipid and lipoprotein concentrations may modify individual responsiveness to alterations in dietary fat and cholesterol content. Objective: The aim was to examine the role of apolipoprotein (apo) B DNA polymorphisms in responsiveness of plasma lipids and lipoproteins to diet. Design: A controlled dietary intervention study was conducted in 44 healthy, middle- aged subjects with a 3-mo baseline, a 1-mo fat-controlled, a 1-mo high-fat, and a 1-mo habitual diet period. We also conducted a meta-analysis of all published dietary trials, including our own. Results: In our own dietary study, the apo B XbaI restriction-site polymorphism affected the responsiveness to diet of the plasma LDL-cholesterol concentration (P < 0.05, repeated-measures analysis of variance). Especially during the high-fat diet, homozygous absence of the XbaI restriction site (X^-/X^-) was associated with a greater increase in LDL cholesterol (44 ± 5%) than was X⁺/X⁺ (27 ± 7%) or X⁺/X^- (40 ± 5%). The high-fat diet also induced a larger increase in plasma LDL cholesterol in subjects with the R^-/R^- genotype (homozygous absence of the EcoRI restriction site) (59 ± 10%) than in those with the R⁺/R^-(39 ± 6%) or R⁺/R⁺ (36 ± 4%) genotype. The M⁺/M⁺ genotype (homozygous presence of the MspI restriction site) was also more responsive (41 ± 3% increase in LDL cholesterol) than the M⁺/M^- genotype (27 ± 10% increase). The meta-analysis supported the finding of the significant role of the EcoRI and MspI polymorphisms, but not that of the XbaI polymorphism. Conclusions: The present study indicated that the apo B EcoRI and MspI polymorphisms are associated with responsiveness to diet.