Approved Research

Impact of genetically determined omega-6/omega-3 ratio on apoB/apoA-1 ratio: a mendelian randomization analysis

Lay summary

The primary purpose of this research is to evaluate the impact of genetic variants and fatty acids on a cardiovascular disease risk marker. Omega-6 and omega-3 are essential polyunsaturated fatty acids derived from the diet. Omega-6 is primarily obtained in the diet from nuts, seeds, and vegetable oils. Omega-3 is primarily obtained in the diet from fish, nuts, and seeds. Previous studies have found genetic associations between the levels of these fatty acids in the body. Omega-6 and omega-3 can impact cardiovascular disease (CVD) risk. One of the most important markers of CVD risk is apolipoprotein B (apoB). ApoB is found on the surface of LDL molecules and is regarded as one of the best measurements for quantifying the amount of circulating LDL particles. ApoA-1 is the main apolipoprotein on HDL and is involved in lipid and cholesterol transport. While increased apoB levels can increase CVD risk, increased apoA-1 levels may be cardioprotective. For this reason, measuring the ratio of apoB-containing particles to apoA-1-containing particles is an important measure of estimating CVD risk.

Various studies have evaluated the impacts of both omega-6 and omega-3 on apoB and apoA-1 levels. Additionally, previous studies have identified genetic variants that impact omega-6, omega-3, apoB and apoA-1 levels. Studies associating omega-6 and omega-3 with apoB and apoA-1 have yielded mixed results. Looking at how genetic variants impact the association between omega-6 and omega-3 levels and apoB/apoA-1 ratio can provide better clarity on the aforementioned relationship. This will be studied in this project via a Mendelian randomization study. The relationship between genetic variants in genes impacting omega-6 and omega-3 levels and measurable omega-6 and omega-3 levels will be assessed. Additionally, the impact of genetically-predicted omega-6 and omega-3 levels on apoB/apoA-1 ratio levels will be measured. Lastly, confounders of this relationship such as fish oil, statins, and vitamins will be assessed.

Understanding the relationship between genetically predicted omega-6 and omega-3 levels can provide better guidance to health professionals and researchers in terms of what genetic variants to assess for in those with elevated apoB levels, what types of dietary strategies to explore that may impact cardiovascular risk, and what types of lab markers to explore in those with cardiovascular disease. The public health impacts of this research can lead to better health education about specific nutritional strategies, as well as, expanding research into specific clinical interventions. The duration of this project will be approximately 6-8 months.