Cholesterol and Genetics - Bad Genes Going for Bad Health

It is a common knowledge that cholesterol and genetics have a very strong link to each other. If you don’t already know that, do yourself a favor and read more. Several studies have already been undertaken to prove this connection and majority of them have found that people who are related to the first degree tend to have similar levels or very close to similar.

Much of the studies regarding the link between cholesterol and genetics have focused on the bad side of cholesterol, specifically on the genetic determinants of low-density lipoprotein (LDL). This cholesterol transporter is the primary cause for the development of atherosclerosis in the blood vessels that is why it has attracted major attention in the scholarly bodies. Clinical studies done specifically for LDL genetic determinants have come to a conclusion that they are, in fact, a heritable trait as evidenced by the relatives (some even used twins) having very close blood LDL values.

Scientists grouped LDL genetics according to pattern of inheritance as seen from the families in the studies. A number of people with high LDL possess a single variant in a gene which affects the LDL. Researchers categorized this single variant pattern of inheritance as autosomal dominant or recessive, Mendelian inheritance being an example. Single variants represent rare cases in familial inheritance but produce dramatic changes in the LDL.

APOB, ABCG5, ABCG8, LDLR, and PCSK9 are all single variants that can radically raise the levels of LDL. They are found in less than 1 out of 500 people but because they produce such effects on the LDL, any individual who carries a mutation of these variants have dramatically increased risk for heart diseases. Familial Hypercholesterolemia, for example, caused by 2 mutations in the variant LDLR can produce profound elevations in the LDL levels by more than 500mg/dL. That’s 400mg/dL more than the optimal level.

The other group is not as clearly defined as the single variants. It does not demonstrate a comprehensible pattern of inheritance, hence more difficult to understand and explain compared to the previous group. On the contrary, this group represents the most part of LDL familial inheritance. The variants produce smaller effects on blood LDL and a possible interaction, a highly complex one at that, has been purportedly seen among numerous genetic variants to produce cumulative effects on the LDL levels.

Variants under the second class include: LDLR (rs688), APOE (rs4420638), APOB (rs693), HMGCR (rs12654264), and PCSK9 (rs11591147). Rest assured that these are no random letters and numbers put together and that I will be writing in English from now on.

Compared to the single variants, these are more common, present in more than 1 out of 100 individuals. Changes in LDL levels aren’t that significant, accounting to roughly 10 mg/dL with every mutation present.

These connections between cholesterol and genetics were derived by several studies, not just one. And basing from them, one can conclude that if a first degree family member presently has or has already died of some cardiovascular disease related to high LDL levels, there’s a chance that you have the same vulnerability and the only thing separating you from that relative is lifestyle and age.