Altered serum lipid level is one of the risk factors for development of cardiovascular disease (CVD)( Reference Musunuru 1 ). Genetic association studies have identified loci in lipid metabolism-related genes such as lipoprotein lipase (LPL) and apolipoprotein E (APOE), which have been shown to be associated with lipid traits( Reference Shatwan 2 , Reference Bennet 3 ). However, very few studies have offered insight into how diet modifies the effect of LPL and APOE single nucleotide polymorphisms (SNPs) on lipids( Reference Carvalho-Wells 4 , Reference Nettleton 5 ). Hence, we investigated the association of common LPL (rs320 and rs328) and APOE SNPs (rs405509, rs439401, rs445925, rs405697, rs1160985, rs1064725, rs7412 and rs429358) with lipids and examined the interactions between the SNPs and dietary factors on lipids in two Caucasian populations. The populations include 664 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) and 1,238 individuals from the Caerphilly study. Statistically significant association was detected between APOE haplotypes (rs7412 and rs429358) and APOE SNP rs445925 and total cholesterol (P = 0·0004 and P = 0·003, respectively). The carriers of APOE E2 allele (5·54± 0·97 mmol/L) had lowest total cholesterol levels compared with E3 allele (5·98± 1·05 mmol/L) (P = 0·001) and E4 allele (6·09± 1·06 mmol/L) (P = 0·0002) carriers, respectively. The association between APOE haplotypes and rs445925 and total cholesterol (P = 0·000002 and P = 0·0003, respectively) were replicated in the Caerphilly study, in addition to the association with LDL-C (P = 0·0004 and P = 0·001, respectively). In the Caerphilly study, interaction between fat (% energy) and rs328 at LPL on triacylglycerol (P = 0·02) and fat (% energy) and APOE haplotype on total cholesterol (P = 0·03) were observed; however, these interactions were not statistically significant after correction for multiple testing. In summary, we have shown that genetic variations at the APOE gene influence plasma lipid concentrations; however, the gene-diet interactions on lipids require confirmation in another larger cohort. The knowledge of combined effect of genetic and dietary factors on lipid profile could help us to a better understanding of the pathogenesis in the CVD.
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