Interaction of PPAR-γ2 gene Pro12Ala single nucleotide polymorphism with dietary intake of fatty acids in determination of plasma lipids in subjects at cardiometabolic risk

Objective: The PPARG SNP rs1801282 (Pro12Ala C>G) has shown variable association with metabolic syndrome traits in healthy subjects. We investigated genotype association with plasma lipids and the influence of dietary polyunsaturated:saturated fat ratio (P:S) in subjects at increased cardiometabolic risk. Methods: Habitual dietary intake was recorded at recruitment to the RISCK Study. PPARG rs1801282 was genotyped in 466 subjects aged 30-70 y. Genotype associations with plasma lipids were assessed at recruitment, after a 4-wk high-SFA (HS) diet and a 24-wk intervention with reference (HS), high-MUFA (HM) and low-fat (LF) diets. The interaction of habitual P:S intake x genotype on plasma lipid concentrations was investigated. Results: PPARG rs1801282 G-allele frequency was 0.09. At recruitment, G-allele carriers had higher plasma total cholesterol concentration (n=415; P=0.05) after adjustment for BMI, gender, age and ethnicity. Dietary P:S ratio x genotype interaction influenced plasma LDLcholesterol (P=0.02) and triglyceride (P=0.03) concentrations. At P:S ratio ≤0.33, mean LDLcholesterol concentration in G-allele carriers was higher than in non-carriers, but fell between 0.34-0.65. Triglyceride concentration followed a similar pattern. After the 4-wk HS diet, Gallele carriers had higher concentrations of total cholesterol (P=0.03), LDL-cholesterol (P=0.04) and apo B (P=0.04) than non-carriers, after adjustments. After the 24-wk interventions, diet x genotype interaction did not significantly influence either LDLcholesterol (P=0.58) or triglyceride (P=0.57) concentrations. Conclusion: A high dietary P:S ratio would help to reduce plasma LDL-cholesterol and triglyceride concentrations in PPARG rs1801282 G-allele carriers at increased cardiometabolic risk.