Interaction between dietary factors and genetic risk for lipoprotein traits and cardiovascular disease

Abstract: In previous studies, a high quality diet has been associated with a reduced risk of cardiovascular disease (CVD) compared to a low diet quality, and specific “healthy” diet components, such as polyunsaturated fatty acids (PUFAs), have been hypothesized to reduce the risk of CVD. However, results from epidemiological studies have been conflicting. This may be due to individuals having varied genetic profiles that are differentially associated with CVD. In genome-wide association studies (GWAS), genetic variations in the fatty acid desaturase gene (FADS1), which encodes the FADS1 enzyme, have been associated with blood lipid and cholesterol concentrations, enzyme activity and concentrations of long-chain PUFAs.

The aim of this doctoral thesis was to examine the interaction between a common genetic variant of FADS1 and the intake of dietary fatty acids with respect to cholesterol concentrations and CVD risk. We also examined whether an overall genetic risk for dyslipidemia can be modified by diet quality and whether diet quality can increase the risk of dyslipidemia and CVD.

We used the population-based Malmö Diet and Cancer study (n=28,098, 61% women) that included baseline examinations that were conducted between 1991 and 1996. The participants' dietary intakes, lifestyle factors, and body compositions were examined, and blood samples were taken. A diet quality index based on the Swedish nutrition recommendations was used to assess diet quality. Incident cases of CVD were identified from registers.

Our results showed that intake of long-chain omega-3 (ω-3) PUFAs can modify the associated effects of FADS1 genetic variations on LDL-C concentrations. The association between FADS1 and reduced LDL-C was observed only among participants who had the lowest intakes of long-chain ω-3 PUFAs. However, genetic variations in FADS1 had little effect on the association between dietary PUFA intake and CVD risk. We also observed that a high quality diet that reflects the Swedish nutrition recommendations might attenuate the association between genetic risk for high LDL-C and increased risk of ischemic stroke compared to a low quality diet. Furthermore, the risk of developing dyslipidemia over 16 years of follow-up was lower in participants who consumed higher quality diets than those who consumed lower quality diets.

In conclusion, our results suggest that it is important to consider gene-diet interactions to understand the etiology of CVD.