Plasma lipids and lipoproteins response to a dietary challenge: analysis of four candidate genes

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Abstract
The possible role of four candidate genes in lipid and lipoprotein response to diet was examined in 63 male students. Four site polymorphisms (signal peptide insertion/deletion, XbaI, MspI and EcoRI) of the apo B gene, three RFLPs (AvaII, StuI, and HincII) of the LDL receptor gene, two SSCPs of the cholesterol 7 alpha-hydroxylase gene and the common apo E genotypes were determined. The average reductions induced by diet in participants homozygous for the absence of the XbaI restriction site (X-X-) of the apo B gene compared to those harboring this site (X+) were: 14.5 mg/dl and 9.4 mg/dl for total cholesterol (TC) (p < 0.09) and 15.5 mg/dl and 7.9 mg/dl for LDL-C (p < 0.003), respectively. Differences in dietary responsiveness among the apo E, LDL receptor and the cholesterol 7 alpha-hydroxylase genotypes were largely insignificant. Using the four apo B polymorphic sites, six unambiguous haplotypes were constructed and a model for their possible evolutionary relationship is presented. Genetic variation in the apo B gene region, as defined by haplotypes, accounted for 8.7% and 24.3% of the phenotypic variance in TC and LDL-C response to diet, respectively. Sequence analysis of a candidate locus, the putative LDL receptor binding region of apo B and its flanking sequences, was performed in two individuals, one homozygous for an apo B "hyper-responding" and another for the "lower-responding" haplotype, and no differences were found. In conclusion, haplotypes at the apo B gene locus are associated with dietary response of TC and LDL-C in young males. Yet, the sequence variation responsible for these differences is possibly located outside the putative LDL receptor binding domain.

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