The peroxisome proliferator-activated receptor α Leu162Val polymorphism influences the metabolic response to a dietary intervention altering fatty acid proportions in healthy men

Abstract

Serum lipid responses to dietary modification are partly determined by genetic factors. We tested whether plasma lipoprotein and lipid responsiveness to a modification in the dietary ratio of polyunsaturated to saturated fatty acids (P:S) is influenced by the peroxisome proliferator-activated receptor alpha (PPARalpha) Leu162Val polymorphism in healthy men. Ten carriers of the V162 allele and 10 L162 homozygotes were matched according to age and body mass index (BMI). During the protocol, all subjects followed the National Cholesterol Education Program Step I diet, but intake of saturated and polyunsaturated fatty acids was adjusted to obtain a P:S of 0.3 for the first 4-wk period (low-P:S diet) and a P:S of 1.0 for the next 4-wk period (high-P:S diet). At screening, the PPARalpha Leu162Val polymorphism was not associated with anthropometric indexes or plasma lipoprotein and lipid concentrations. After the high-P:S diet, a significant gene-by-diet interaction was observed for changes in plasma total cholesterol, apolipoprotein (apo) A-I, and cholesterol concentrations in small LDL particles (P <or= 0.05). Mean differences after the high-P:S diet were observed between genotype groups for plasma apo A-I concentrations (P<0.05). Changes in BMI, waist circumference, and concentrations of triacylglycerol, phospholipid, and apo B did not differ significantly between groups. The PPARalpha Leu162Val polymorphism may contribute to interindividual variability in plasma lipoprotein and lipid response after modification of the dietary P:S ratio.