The contribution of candidate genes to the response of plasma lipids and lipoproteins to dietary challenge.

The possible role of four candidate genes in lipid and lipoprotein response to diet was examined in 214 members of two large kibbutz settlements in Israel. Four site polymorphisms (signal peptide insertion/deletion, XbaI, EcoRI and MspI) of the apo B gene, the common apo E genotypes, three common mutations (T-93G, S447stop and N291S) of the LPL gene and the CETP I405V RFLP were determined. The average reduction induced by diet in participants with the absence of the EcoRI restriction site (L4154) of the apo B gene compared with those found to be homozygotes for the restriction site (G/G4154) were: 16.2 and 8.0 mg/dl for total cholesterol (TC) (P=0. 01); and 15.6 and 6.2 mg/dl for LDL-C (P=0.007), respectively. TC and LDL-C baseline levels were significantly different among the apo-E genotypes, yet there were no significant effects on lipid and lipoprotein dietary response. Triglyceride baseline values were significantly lower (P=0.007) among subjects with the LPL S447stop mutation and HDL-C was significantly lower (P=0.008) among subjects found to be heterozygous for the LPL N291S mutation. A heterogeneous response for triglyceride was observed for individuals with the S291 allele as compared to those individuals who were found to be homozygous for the N291 allele. No differences in dietary responsiveness were observed among the apo E and CETP genotypes. In conclusion, our results suggest that sequence variation(s) in the coding region of the apo B gene linked to the EcoRI polymorphism are associated with total cholesterol and LDL-C responsiveness to dietary manipulation. In our study population, LPL mutations had a significant effect on TG and HDL-C baseline levels and on their response to diet.