A genetic variant of PPARA modulates cardiovascular risk biomarkers after milk consumption

Objective: The association of dairy food consumption with the risk for developing cardiovascular disease (CVD) has been investigated in many studies, but results often have been contradictory. The aim of the present study was to determine whether genetic polymorphisms are associated with interindividual variation in the response of CVD risk biomarker values after milk consumption. Methods: Fourteen single nucleotide polymorphisms (SNPs) in nine genes related to lipid metabolism were examined in 161 volunteers randomly allocated to consume either 500 mL/d of skimmed (S) or semi-skimmed (SS) milk for 1 year in addition to their usual diets. Total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and low-density lipoprotein/HDL-C ratios were used as biomarkers of CVD risk. Three-way repeated-measures analysis of variance was used to examine the effect of time, treatment (S or SS), and genotype on these biomarkers. Results: A TT genotype for the proliferator-activated receptor alpha polymorphism (PPARA rs135549 SNP) was significantly associated with a reduction in the TC/HDL and LDL/HDL ratios after 12 mo of S milk intake (mean reduction -0.29, 95% confidence interval [CI], -0.63 to 0.05; P= 0.0015 and -0.31, 95% CI, -0.58 to -0.03; P = 0.0005, respectively). However, no differences were observed after consuming either S or SS milk in the C allele carriers. Conclusions: Saturated fatty acid consumption has long been linked to an increased risk for CVD; indeed, the consumption of saturated fat-free products is recommended as a means of reducing this risk. However, the present results suggest that many individuals might not benefit from such general recommendations. Genetic analysis of PPARA rs135549 might help identify those individuals who are more likely to benefit from reducing the saturated fatty acid content of their diet.