Genetic variation at the apolipoprotein gene loci contribute to response of plasma lipids to dietary change.

Dietary intervention studies (from a low polyunsaturated/saturated fatty acid ratio P/S diet to a high P/S diet), carried out on a group of healthy individuals from North Karelia, Eastern Finland between 1981-1984, provided evidence that there may be a genetic component contributing to variation in response to dietary change. We have resampled blood from 107 individuals involved in the original studies and used Restriction Fragment Length Polymorphisms (RFLPs) to study the genetic contribution of variation at a number of candidate gene loci to the response to dietary change. The genes investigated in this study were the apolipoprotein (apo) genes: apo B, apo AII, apo E (protein polymorphism), apo AI-CIII-AIV gene cluster, and the LDL-receptor gene. On the basal diet the major effect of genotype on lipid traits was due to variation at the apo E gene locus; this protein polymorphism explained 14.6% of the phenotypic variance in LDL cholesterol levels and 12.7% of the phenotypic variance in total cholesterol levels. When switched to low fat high P/S diet, these effects of variation at the apo E gene locus on the phenotypic variation of LDL and total cholesterol levels disappeared. The major effect on the response to dietary change, delta, was seen on the difference in apo AI levels mediated by variation at the apo B gene locus (MspI RFLP) explaining 6.3% of the phenotypic variance in apo AI change. For the RFLPs of the apo AI-CII-AIV gene cluster, small but not significant differences on delta were found. Our results indicate that within the limits of the candidate genes studied, the major effects in response to dietary change was on apo AI levels mediated through variation at the apo B gene locus.