The lipoprotein/lipid profile is modulated by a gene–diet interaction effect between polymorphisms in the liver X receptor-α and dietary cholesterol intake in French-Canadians

Genetic and nutritional factors interact together and modulate the plasma lipid profile. We identified variations in the gene encoding the liver X receptor alpha (LXRalpha) and investigated their effects on the plasma lipoprotein/lipid profile. We also examined whether the association between cholesterol intake and plasma lipid profile was modulated by LXRalpha variants. The LXRalpha gene was sequenced in thirty-five French-Canadian men with high plasma total cholesterol (>5.0 mmol/l) and LDL-cholesterol (>3.5 mmol/l) concentrations. dietary cholesterol was obtained from a food-frequency questionnaire. The LXRalpha c.-115G>A, c.-840C>A and c.-1830T>C genotypes were determined by direct sequencing in 732 subjects. Molecular screening of the LXRalpha gene revealed sixteen variants. Genotypes c.-115G>A, c.-840C>A and c.-1830T>C (rare allele frequency of 14.3%, 14.2% and 11.0%, respectively) were analysed further. Plasma total cholesterol concentrations were higher in carriers of the -115A, -840A and -1830C allele, compared with the -115G/G, -840C/C and -1830T/T homozygotes (P< or =0.05). In a model including the c.-115G>A polymorphism, cholesterol intake, the interaction term c.-115G>A x cholesterol intake (mg/d) and covariates, LXRalpha-115G>A explained 1.8% and 2.1% of the variance in total cholesterol and LDL-cholesterol concentrations (P=0.02 and P=0.01), whereas the interaction term explained 2.9% (P=0.002) and 2.8% (P=0.005), respectively. When subjects were divided into four groups according to the median of cholesterol (290.8 mg) and -115G>A genotypes, high cholesterol intake was associated with higher cholesterol levels in -115A carriers. Similar results were observed for c.-840C>A and c.-1830T>C. These results suggest that cholesterol intake interacts with LXRalpha variants to modulate the plasma lipid profile.