Genetic testing isn't a crystal ball for your health

Choosing Wisely Australia has released its latest recommendations on the use of genetic testing, suggesting people avoid genetic tests for Alzheimer’s (APOE), coeliac disease and folate conversion (MTHFR).

Testing these genes is not recommended as results do not lead to improved health outcomes, and may create anxiety or false hope among patients.

Led by Australia’s health colleges, societies and associations and facilitated by NPS MedicineWise, the Choosing Wisely initiative drives conversations for the health care community and consumers about eliminating the use of unnecessary and sometimes harmful tests, treatments, and procedures.

Genetic testing as a health care tool

Genetic testing is currently available for more than 2,000 rare and common conditions. It is an important tool for the diagnosis of rare and inherited conditions such as cystic fibrosis. It can also guide health care and decisions for families with a strong history of cancer and high cholesterol.

However, its use it not always justified.

Genetic testing involves analysis of a person’s DNA: it looks for variants in genes that have an impact on our health. However many variants do not have a strong association with disease. Indeed, for many we don’t know what affect they have at all.

When the evidence for an association between a genetic variant and a health outcome is weak, genetic testing does not add any value for the health professional in making decisions about treatment and patient management. This reflects the fact that gene variants are common in our DNA and often not responsible for disease symptoms.

MTHFR and APOE are examples of genes with known and common variants that are poorly correlated with predicting future health risks.

Genetic testing to assess folate conversion

Folate and folic acid are forms of the vitamin B9. The MTHFR (5,10-methylenetetrahydrofolate reductase) gene is involved in converting the vitamin into a form the body can use.

There are two common variants in the MTHFR gene, and 60–70% of the general population will have at least one of these variants.

People with MTHFR variants still usually convert sufficient folate for the body to function as normal. With a good diet, the effects of a MTHFR variant can be easily overridden.

Low levels of folate are known to increase the risk of neural tube defects, where part of a baby’s brain or spinal cord does not form correctly during pregnancy. Australian women are advised to take folic acid for a minimum of one month before conception and for the first three months of pregnancy, irrespective of their MTHFR gene variant status.

Although variants in the MTHFR gene have been suggested to play a role in some blood clotting disorders and heart disease, there is insufficient evidence to show that MTHFR variants have any significant impact on these conditions.

Even though folate deficiency in Australia is rare, and people with variants of MTHFR can still convert sufficient folate for good health, there has been a rapid increase in consumer-driven MTHFR gene testing as part of “healthy lifestyle” testing.

GPs and genetic clinics also report high levels of anxiety among clients seeking clinical advice about their MTHFR test results.

MTHFR genetic testing is not recommended.

Genetic testing for Alzheimer’s disease

There are a number of well known variants in the APOE (apolipoprotein E) gene. The APOE E4 form of this gene is often suggested to have a connection with the late-onset form of Alzheimer’s disease, affecting people aged 60 years and over.

However this variant has been found in healthy members of the community as well as those who develop Alzheimer’s disease. Until more is known about the role of the APOE gene, determining which form of the gene is present can’t predict accurately whether a person is predisposed to develop the condition.

Current genetic tests that claim to predict risk of Alzheimer’s disease based on APOE are therefore limited and unlikely to do anything other than create unnecessary anxiety.

It can also create a false sense of security because late-onset Alzheimer’s disease also develops in people who don’t carry the APOE E4 variant.

But familial factors do influence the risk of dementia. People with dementia occurring in later life – of which Alzheimer’s disease is the most common form – are about three times more likely to have a parent or sibling with dementia.

Late onset Alzheimer’s disease must not be confused with a very rare form of early onset familial Alzheimer’s disease. Symptoms usually start well before 65 years of age and genetic testing of particular genes may be considered for this specific condition.

Genetic testing for coeliac disease

Coeliac disease is a condition in which the immune system is abnormally sensitive to gluten, a protein found in wheat, rye and barley. When coeliac disease is not well managed it can lead to diarrhoea, fatigue, weight loss, bloating and anaemia, and more serious complications.

Although variants in genes that provide instructions for making proteins in the immune system can indicate an increased risk of developing coeliac disease, this field of research is still relatively young.

The new Choosing Wisely Australia recommendation reflects The Gastroenterological Society of Australia’s view that a genetic test should not currently be used to diagnose coeliac disease. Professor Anne Duggan from the society says,

As a coeliac gene can be found in one-third of the population and a positive result does not make coeliac disease a certainty, serological testing is the appropriate first-line screening tests for coeliac disease.

Serological testing measures levels of specific antibodies in blood, and can be followed up with intestinal biopsies for confirmation.

Consumer driven genetic testing

Clear health benefits have come from the rapid development of genetic technologies and increased availability of genetic testing. However, genetic tests are complex. Results often require interpretation from an experienced practitioner, as they have multiple possible outcomes and levels of certainty.

When health consumers undertake testing without the involvement of a health professional, there is potential for misinterpretation of results, inappropriate further investigations and treatment, unnecessary anxiety and false reassurance.

Genetic testing results can have implications for family members due to the shared nature of genetic information in families. Misinterpretation and anxiety may be exacerbated as results are relayed to relatives.

With the increase trend towards direct-to-consumer testing – where tests are purchased directly by consumers, often over the internet and usually without the involvement of a health professional – and the translation of testing into mainstream medicine, guidelines from Choosing Wisely Australia are timely.

With the advent of new technologies, we must be circumspect about the validity of testing and over-testing and aim to avoid causing patients and their families unnecessary harm.

Genetic testing is best performed in a clinical setting with the provision of personalised genetic counselling and professional interpretation of tests results.

Kate Dunlop receives funding from NHMRC.