Genetic predisposition influences plasma lipids of participants on habitual diet, but not the response to reductions in dietary intake of saturated fatty acids

C.G Walker,R.J.F Loos,A.D Olson,G.S Frost,B.A Griffin,J.A Lovegrove,T.A.B Sanders,S.A Jebb

doi:10.1016/j.atherosclerosis.2010.12.039

Abstract

ObjectiveSNPs identified from genome-wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the ‘RISCK’ study cohort. MethodsParticipants (n=490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. ResultsThe associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total (P=0.02) and LDL (P=0.002) cholesterol, triglycerides (P=0.001) and apolipoprotein B (P=0.004), and with lower baseline concentrations of HDL cholesterol (P<0.001) and apolipoprotein A-I (P<0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. ConclusionResults from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.

Highlights

Plasma lipids are risk factors for cardiovascular disease (CVD) and are known to be sensitive to dietary change [1]
Each additional risk-allele in the TC-genetic predisposition score (GPS) was associated with 0.08 mM higher TC concentration; the LDL cholesterol (LDL-C)-GPS was associated with a 0.06 mM higher LDL-C concentration per additional risk-allele and the TG-GPS with a 0.04 mM higher lnTG concentration per additional risk-allele (Table 2)
The LDL-C-GPS was associated with higher apolipoproteins B (apo B) concentration and the HDL cholesterol (HDL-C)-GPS with lower apo A-I levels per additional risk allele (Fig. 1)

Summary

Introduction

Plasma lipids are risk factors for cardiovascular disease (CVD) and are known to be sensitive to dietary change [1]. Genome-wide association (GWA) studies have identified a number of SNPs robustly associated with traits of dyslipidaemia in cross-sectional studies [9,10,11,12,13,14,15,16] It remains unknown whether these common lipid-associated SNPs alter the responses to dietary interventions. We hypothesised that the mechanisms underlying genetic predisposition to dyslipidaemia would impair the improvement in plasma lipid status which can be produced by modifying the amount and type of dietary fat This hypothesis was tested in a cohort of 490 participants in the RISCK trial; a highly controlled intervention to reduce dietary saturated fat based on replacement with either carbohydrate (CHO) or monounsaturated fat (MUFA) [2]. We examined the association of 39 lipid-associated SNPs, individually as well as combined, on plasma lipid measures at baseline

Methods

Results

Conclusion