Analyzing the risk of cardiovascular disease from a genetic perspective (1): From the liver to the heart

introduction

We may have heard of such a tragedy many times.

Chapter 1: From the liver to the heart

Myocardial infarction seems to have a sudden onset, but before the onset, the patient’s blood vessels have been narrowed due to atherosclerosis.

To blame for genes

Whenever someone heard that a public figure died of a heart attack, everyone would first blame him for his unhealthy diet, insufficient exercise, or too much work pressure and not paying attention to other life factors such as rest.

Liver, cardiovascular disease risk genes are concentrated

Cardiovascular diseases seem to be in the heart, but the genes that cause problems are mainly expressed in the liver.

Figure 1.

LDLR, APOB, PCSK9, APOE, LPA, SCARB1 and APOA1 are mainly expressed in the liver.

We already know that atherosclerosis is the cause and prelude of most cardiovascular diseases.

Figure 3.

Low-density cholesterol LDL-C

The first blood indicator, LDL-C, is what we usually call "bad" cholesterol.

Familial hypercholesterolemia

Familial hypercholesterolemia (FH) is currently the most studied genetic disease with the strongest correlation with cardiovascular disease.

Figure 3.

High Density Cholesterol HDL-C

The second blood indicator HDL-C, which is what we often call "good" cholesterol.

Figure 5.

Lipoprotein a-Lp(a)

The third blood index Lp(a), called Lp little a, is a variant of LDL particles.

In addition to the familial hypercholesterolemia genes mentioned above, mutations in genes such as APOE, ABCG5/ABCG8 can also cause symptoms similar to hypercholesterolemia and severely increase the risk of cardiovascular disease.

In addition, genes related to vasodilation, oxidative free radical scavenging, endothelial cell function, high triglycerides, obesity, type 2 diabetes, and other related genes may affect the risk of cardiovascular disease.

Figure 5.
Biological pathways and risk genes related to atherosclerotic cardiovascular disease.

Battle of fate

Cardiovascular and cerebrovascular diseases seem to be in the heart and brain, but the problem is mainly in the liver.
This is because the liver is responsible for the scheduling and management of the cholesterol supply chain in the body.
Once the cholesterol management is out of question, the cholesterol concentration in the blood will be Elevated, the process of atherogenesis will be accelerated, and eventually lead to myocardial infarction or various ischemic cardiovascular and cerebrovascular diseases.

Mutations in the LDLR, APOB and PCSK9 genes can cause familial hypercholesterolemia.
The functions of these genes are all around the liver's transport and recovery of cholesterol.
If people with these gene mutations are not diagnosed in time and seek cholesterol-lowering treatment, the risk of cardiovascular disease will be 10-20 times that of ordinary people.
However, clinical follow-up experiments have shown that if genetic mutation carriers are diagnosed in their adolescence and take cholesterol-lowering drugs and dietary treatments, the risk of cardiovascular disease can be greatly reduced, and the time for cardiovascular disease to appear will be longer than if it was not.
The person treated is 10-15 years late.
Approximately 1/100-1/200 people may carry such pathogenic mutations.

Mutations in the APOE gene can cause type 3 hyperlipidemia, and these people have 5-10 times more premature cardiovascular events than ordinary people.
Changing diet can be very effective in lowering human-like cholesterol.
However, although the popular ketogenic diet is very effective for weight loss, it will also increase the cholesterol of people with APOE gene mutations and increase the risk of cardiovascular disease.
Less than 1% of the population carry the type 3 hyperlipidemia mutation.

Short variants of the LPA gene are the genetic risk of cardiovascular disease with the largest number of people.
About 20% of the European and American populations, and a few among the Chinese, about 5-7% have this variant.
The LPA short variant is related to the increase of Lp(a) in the blood.
It is an independent risk factor that can increase the risk by an average of two times on the basis of other existing risk factors (such as high cholesterol).
There are no good drugs to lower Lp(a), and neither diet nor exercise can lower Lp(a).
However, many pharmaceutical companies are now prescribing RNAi Lp(a) lowering drugs, and it is expected that there will be effective drugs for this most common cardiovascular disease genetic risk in the near future.

In addition, the genes APOA1, ABCA1, CETP, LCAT and SCARB1 related to cholesterol reversal can increase or slow down atherosclerosis.
The expression of these genes can be regulated by phytoestrogens in tofu, and some can be regulated by green leafy vegetables.
The vitamin A in red radish can be regulated by drinking or not, and some can be regulated by the lecithin in the egg yolk.
In short, if the diet and nutrition are applied correctly, it will have a great risk of atherosclerosis and cardiovascular disease.
change.

Each of us will more or less carry various degrees of risk variants, and the combination of these risk variants constitutes different levels of intermediate risk.
Some people have a poor genetic combination, coupled with poor living habits, and symptoms of cardiovascular disease appear earlier.
Some people are particularly lucky, with the best genome and, coupled with good living habits, live to 100 Cardiovascular and cerebrovascular can still work normally.
For most people, if they do not die of cancer, they will not be able to escape from cardiovascular and cerebrovascular diseases sooner or later.
Those who are particularly long-lived are those who have escaped from cancer and escaped from cardiovascular and cerebrovascular diseases.
Slowing down the process of atherosclerosis is the only way to longevity and health.

Although we cannot change our genes, it is "fate", but we can seek the best way out for our health and pursue the best "luck" through in-depth understanding of the pathogenic mechanism.
Today, with the development of medical biology, we have the opportunity to use knowledge as a weapon to change our destiny.

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