Summary

Biochemical testing combined with genetic screening is increasingly used by doctors to inform clinical and therapeutic decision making in the risk management of chronic and degenerative diseases. It is well known that increased cholesterol levels are associated with heart attacks and Alzheimer’s disease. It has recently been demonstrated that certain genetic markers can be responsible for these increased cholesterol levels when they are activated by obesity or environmental influences such as an unhealthy diet. For instance, the cholesterol-raising apolipoprotein E (APOE) polymorphism (ɛ-4 allele) provides a link between cardiovascular disease (CVD) and Alzheimer’s disease. This genetic alteration is present in about 25% of the general population. People with the APOE ɛ-4 allele do not experience the same protection from CVD related to alcohol consumption than those without this genetic variation. Knowledge of this genetic marker enable doctors to warn their patients to limit their alcohol consumption to reduce the risk of CVD and Alzheimer’s disease.

CHOLESTEROL_THUMBNAIL

Modern Western medicine made spectacular advances in the past millennium in the treatment of acute, life-threatening diseases presenting as medical or surgical emergencies. Most acute infections can be treated with modern antibiotics, and serious injuries and other surgical emergencies such as acute appendicitis, can effectively be treated with life-saving operations due to safe anaesthetics and sterile operating procedures.

Unfortunately, the same is not true for the modern epidemic of the chronic and degenerative diseases due to unhealthy lifestyles and adverse environmental conditions. Despite the advances made in the discovery of new medicines and lifesaving operations, modern medicine does not have all the answers for these lifestyle-related conditions caused mainly by the destructive lifestyle of modern man. The pharmaceutical industry developed medicines for the management of diseases such as diabetes, CVD, arthritis, osteoporosis and cancer. Patients also insisted on medicines to cure all their ailments without taking responsibility for their own health. Unfortunately, most of these medications relieve the symptoms only, and do not cure these diseases except if the real cause is addressed where possible. Some of these medications such as the anti-inflammatory medicines and cholesterol-lowering agents may cause serious and life-threatening side effects in some people due to differences in their genetic make-up. The Medicines Control Councils were forced to recall some of these common approved prescription medicines due to unforeseen fatalities and serious side effects.

Medical scientists realised that more should be done to prevent these lifestyle-related diseases before it became manifest, rather than to rely on medicines only to treat these conditions. These chronic and degenerative diseases develop over a period of several years, and doctors identified various factors contributing to the development of these diseases. Epidemiological data identified several associations of these chronic diseases with factors such as smoking and air pollution, obesity, inactivity, unhealthy diet and alcohol abuse, as well as ultraviolet irradiation. Great advances were made in the development of biochemical tests to identify early manifestations of diabetes and heart diseases. Abnormalities in glucose- and cholesterol metabolism can be detected years before a heart attack or the manifestation of diabetes mellitus. This enabled doctors to introduce the necessary lifestyle modifications such as diet interventions, exercise and weight loss programmes, as well as certain supplements to restore the homeostasis in the body without only relying on medications.

The unravelling of the human genome in 2003 brought a new dimension in the diagnostic and therapeutic armamentarium of the modern doctor. Major and minor genetic abnormalities were detected to identify the cause of specific diseases in families and individuals. Certain genetic abnormalities could be linked to specific diseases, and it was also established that certain abnormal biochemical results are also linked to a genetic profile. Clinical features such as overweight and high blood pressure could also herald the risk to develop serious diseases. The combination of related clinical-, biochemical- and genetic-information became a valuable decision-making tool in the management of these chronic and degenerative diseases. In this research project we demonstrated that genetic testing should not be done in isolation, but must be combined with a lifestyle questionnaire, including the family history and careful analysis of the diet and alcohol consumption.

The determination of cholesterol levels is of particular importance in South Africa, where the prevalence of familial hypercholesterolaemia (FH) is increased 5 to 10 times, compared to most other populations in the world due to a founder effect. This led to the development of a genetic test by our laboratory for FH to identify these patients with a high risk of cardiovascular disease. These patients need urgent treatment with cholesterol-lowering agents to prevent a premature heart attack, despite their APOE status.

It is well established that abnormal cholesterol levels are also associated with cardiovascular disease and Alzheimer’s disease in people that do not suffer from FH. We demonstrated that certain minor genetic markers could cause elevated cholesterol levels when they are activated by overweight, inactivity and an atherogenic diet. The cholesterol-raising apolipoprotein E (APOE) polymorphism (ɛ- 4 allele) provides a link between cardiovascular disease (CVD) and Alzheimer’s disease. This genetic alteration is present in about 25% of the general population. Our previous research demonstrated that moderate intake of alcohol protects people from CVD. However, people with the APOE ɛ- 4 allele do not experience the same protection from CVD than those without this genetic variation. Knowledge of this genetic marker enable doctors to warn their patients to limit their alcohol consumption to reduce the risk of CVD and Alzheimer’s disease.

What does this research mean for the wine-loving community

The good news is still valid; moderate and responsible wine consumption provides some protection against the development of cardiovascular disease. This is supported by various epidemiological and experimental observations worldwide, despite the very negative comments made in the UK recently about the adverse effects of alcohol. Of course we assume that the moderate and regular consumption of wine is associated with a healthy lifestyle including a balanced diet, weight management, no smoking, and regular exercise.

However, genetic testing enabled us to detect people with elevated cholesterol suffering of FH. Our laboratory identified that most people with FH goes undetected, because of the unavailability of genetic testing procedures. They are at risk to develop cardiovascular disease, and need urgent treatment with cholesterol-lowering agents to prevent this catastrophe, irrespective of APOE status. In contrast, people without FH, but with the cholesterol-elevating APOE polymorphism (ɛ-4 allele), respond better to lifestyle modification such as diet, weight loss, and exercise than on cholesterol-lowering agents such as the statins. This has important implications, because it has recently been demonstrated that statins have various negative side effects in some patients such as muscle pains due to muscle breakdown. The use of statins is also implicated in the development of cerebrovascular attacks in these patients. People in this genetic subgroup should therefore not be treated with these potential toxic medications such as the statins. Alcohol abuse should also be avoided in this subgroup of patients, because they do not derive the same cardioprotective benefits than people with a normal genetic profile.

Conclusion

Chronic and degenerative diseases as the result of a destructive lifestyle derive more benefit from lifestyle interventions rather than medications. In fact, some of the current prescription drugs for these diseases do have serious side effects, and efforts should be made to detect biochemical and genetic markers to guide us in our search for more appropriate therapy.

However, certain inherited diseases such as FH, needs urgent identification and aggressive therapy. Our research also indicated that many people with FH remain undetected, because the genetic profile is unknown. Patients with abnormally high cholesterol and a family history of CVD, need to undergo genetic testing.

Moderate and regular alcohol intake, and more specific red wine, in conjunction with a balanced diet and a responsible lifestyle, provides health benefits to the majority of the population. Personal and family history, in conjunction with biochemical blood analysis and certain genetic testing, provides a scientific platform for doctors to diagnose and treat these conditions more appropriately.

– For more information, contact Dr. David van Velden at dpvv@sun.ac.za.

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