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Interaction Between Genetic and Environmental Factors in Atherosclerosis

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Atherosclerosis can be instigated by a variety of genetic and environmental factors. Individually environmental and genetic risk factors and how they affect atherosclerosis are understood. However, the understanding of how a genetic condition interacts with environmental factors is less understood. In this essay the interactions between Familial Hypercholesterolaemia (FH) and environmental factors interact and there consequences will be discussed.

FH is an autosomal codominant disease, it is inherited and affects the metabolism of lipoproteins (Ramaswami et al., 2019). FH is characterised by a mutation in the Low-density lipoprotein receptor (LDLR) gene, it affects up to 1 in 500 people worldwide (Wierzbicki, Humphries and Minhas, 2008). The disease is defined by very high plasma concentrations of low-density lipoproteins cholesterol (LDL) (Pimstone et al., 1998). The mutation of the LDLR gene is what causes the extremely high levels of LDL. This is because the defect can affect several vital steps in the receptor cycle, for example it inhibits the correct binding of LDL, the internalisation and the recycling of LDL also (Pimstone et al., 1998).

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Understating the relationship between FH and environmental factors have been shown by using murine models, work by Ma. Y et al. shows two groups of homozygous LDLR knockout mice which were put on different diets. One group was fed a high fat diet (HF), and the other group were put on a regular chow diet (Ma et al., 2012). The total cholesterol and LDL levels of the mice on the HF diet increased dramatically over the first two weeks, this was then followed by a slower increase to the terminus after the twelve months (Ma et al., 2012). The HDL of the mice on the HF diet were elevated slightly and the triglyceride quantity did not increase drastically (Gomez et al., 2019). In comparison the mice that were on the regular chow diet plasma lipid levels were maintained for the whole 12 months. HF diet mice after 3 months had LDL levels of approximately 10 mmol/L, non-HF diet mice after 3 months had an LDL value of approximately 4mmol/L (Ma et al., 2012). This shows that even if you have FH eating a HF diet will further increase your risk of atherosclerotic lesions forming. This is because the main starting point of atherosclerosis is when the circulating LDL value is increased. There is however an argument for using mice, due to their inability to develop unstable plaques, and their reduced ability to develop plaques in the coronary arteries, but due to their notable work towards the understanding of atherosclerosis murine models are vital for research.

Further work undertaken by Frederick J. Raal et al, investigates whether lipid lowering drugs, predominately statins, reduce cardiovascular mortality in homozygous FH patients. To evaluate the efficiency fasting serum concentrations of total cholesterol, LDL, HDL and triglycerides were taken (Raal et al., 2011). The results of the research show that the patients who had received the new modern lipid lowering therapy showed a notable reduction in mortality (Raal et al., 2011). The data further suggested that even though LDL remained high, using statins delayed cardiovascular events for homozygous FH patients. This study did however have its faults, for example they only had 187 subjects, this is not enough and to improve validity an increased population size would is necessary. The research was also only undertaken in South Africa, so again to make the in research more valid they should do it in other countries to ensure results are not down to an ethnic predisposition (Martínez-Mesa et al., 2014).

In conclusion having FH and eating a HF diet leaves you at a greater risk of atherosclerosis. This indicates that there is a clear interaction between both genetic and environmental factors working together in atherosclerosis.

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Interaction Between Genetic and Environmental Factors in Atherosclerosis. (2022, August 25). Edubirdie. Retrieved February 8, 2023, from
“Interaction Between Genetic and Environmental Factors in Atherosclerosis.” Edubirdie, 25 Aug. 2022,
Interaction Between Genetic and Environmental Factors in Atherosclerosis. [online]. Available at: <> [Accessed 8 Feb. 2023].
Interaction Between Genetic and Environmental Factors in Atherosclerosis [Internet]. Edubirdie. 2022 Aug 25 [cited 2023 Feb 8]. Available from:
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