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 Is rael. Four site polymorphisms (signal peptide insertion/deletion, XbaI, Eco RI and MspI) of the apo B gene, the common apo E genotypes, three common mu tations (T-93G, S447stop and N291S) of the LPL gene and the CETP I405V RFLP were determined. The average reduction induced by diet in participants wit h the absence of the EcoRI restriction site (L4154) of the apo B gene compa red with those found to be homozygotes for the restriction site (G/G4154) w ere: 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 level s were significantly different among the apo-E genotypes, yet there were no significant effects on lipid and lipoprotein dietary response. Triglycerid e 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 heterogene ous response for triglyceride was observed for individuals with the S291 al lele as compared to those individuals who were found to be homozygous for t he N291 allele. No differences in dietary responsiveness were observed amon g the apo E and CETP genotypes. In conclusion, our results suggest that seq uence variation(s) in the coding region of the apo B gene linked to the Eco RI polymorphism are associated with total cholesterol and LDL-C responsiven ess to dietary manipulation. In our study population, LPL mutations had a s ignificant effect on TG and HDL-C baseline levels and on their response to diet. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.