INFLUENCE OF MUTATION IN HUMAN APOLIPOPROTEIN A-1 GENE PROMOTER ON PLASMA LDL CHOLESTEROL RESPONSE TO DIETARY-FAT

The plasma lipid response to changes in dietary fat and cholesterol can vary between individuals. At present, responders cannot be identified in advance. An adenine to guanine (A-->G) mutation in the promoter of the apolipoprotein A1 gene (apoA-1) has been suggested as affecting plasma high-density lipoprotein cholesterol. In 50 young men we examined the effect of the same mutation on the responses of both high and low density lipoprotein cholesterol to low-fat diet. The frequency for the A allele was 0.14. Subjects were fed a low-fat diet for 25 days, followed by a diet rich in monounsaturated fatty acid (MUFA, 22% out of 40% fat) for 28 days and lipoproteins were measured at the end of each diet. There were no differences in initial total cholesterol between subjects with the G/G mutation (170 mg/dL: 100 mg/dL= 2.59 mmol/L)) and the G/A mutation (169 mg/dL) genotypes. After consumption of the high monounsaturated fat diet, significant increases were noted in plasma LDL cholesterol (10 mg/dL, p=0.035) in the G/A subjects but not in the G/G subjects (1 mg/dL, p=0.996). These differences showed that a significant diet-gene interaction (p=0.015) existed. No differences were observed on HDL cholesterol between groups. Plasma low-density lipoprotein cholesterol responsiveness to diet may be explained by variation at the apoA-1 gene locus.