Meet your genes

All your life you live with the notion that you got this from your mother and that from your father. You never quite know though. Your genes, your most basic building blocks remain a mystery.

A while ago I gave a pin-prick of blood, and a few weeks later I was looking at a piece of paper telling me that I do not have the APO E4 genetic variation – it is one of the mutations that most strongly indicate you’re at risk of developing Alzheimer's disease.

There was certainly some comfort in not having APO E4. But what really got to me was seeing my genetic information down on paper. There is something moving about seeing part of the formula that underpins your physical existence summarised on a piece of paper like that; something akin to a loss of innocence.

The test
I had the nutrigenetic wellness screen done with a local company called Gknowmix. Doctors, dieticians and geneticists make up the professional team.

I had to fill in a long questionnaire on my lifestyle and medical history; and a drop of blood was sent to Molecular Diagnostic Services (MDS) in Durban to be examined using polymerase chain reaction (PCR)-based methods. The results were then matched to my lifestyle and medical information, and turned into a comprehensive report, complete with lifestyle and dietary recommendations.

This report was then discussed with me by a medical doctor, Dr Badenhorst. Depending on how you go about it, this consultation could also be done by a registered dietician.

What the report said
Overall, apparently, I have good genes – at least as far as the limited scope of the test I did goes. My test basically looked for about ten or so "spelling errors" in key genes. These are mostly things called single nucleotide polymorphisms (where the letters that make up a specific stretch of DNA get mixed up) or deletions (where genetic material is simply missing).

The test did, however, find that I have an “error” – a genetic variation in the methylenetetrahydrofolate reductase ( MTHFR) gene, which is involved in homocysteine and folate metabolism. An estimated 25% of South Africans have this variation, which ups the odds of having high levels of homocysteine in your body. High homocysteine levels are associated with an increased risk of developing heart disease, although it hasn't been proven that high homocysteine levels actually cause the increased risk.

According to my report, "the MTHFR gene indicates an increased requirement of folate to prevent homocysteine accumulation and DNA damage."

End result? Because I have this particular MTHFR variation it, is recommended that I have a daily intake of 800 ug of folic acid, as opposed to the normal recommended daily allowance of 400 ug.

To some extent at least, it seems that personalised medicine has arrived.

On the whole though, recommendations generally don't stray far from the standard advice of lots of exercise, not smoking, and eating a balanced diet with lots of green leafy vegetables. Mostly the evidence for straying from these basic recommendations on the basis of genetic markers is still very sketchy.

Where it all fits in
It so happened that I did a follow-up interview with Dr Badenhorst in a hotel lobby at Grand West casino, where he was staying while attending a conference in the Cape.

But whereas the slot machines are rigged to take your money, and the best you can hope for is a bit of luck against the odds, the lottery of your genes is no longer just the hand that's been dealt. To push the metaphor some more, we can, with genetic testing, see what cards we're holding; and we're slowly learning how to play poker.

"If you optimally manipulate your environment – the food you eat, the exercise you do, the water you drink, the vitamin supplements; if you get all that optimally, you can manipulate those ‘spelling errors’ you got from mom and dad. If you want to put it that way, switch them off," says Badenhorst.

This is true of so-called low-penetration genetic variations, where the risk that a particular variation poses can be mitigated by environmental factors or other genes. So, for example, having he Apo E4 variation does not mean you'll necessarily develop Alzheimer's disease or high cholesterol. If you are lucky with the rest of your genetic make-up, and you do lots of exercise and avoid smoking and alcohol, you may cut the risk by a substantial margin.

Other examples of health issues related to low penetration genetic variations are clotting, heart disease, iron problems, cancer, and overweight.

By contrast, there is hardly anything you can do to ward off the consequences of a high-penetration genetic variation like that for Huntington’s disease.

Part of a picture
According to Badenhorst, nutrigenetic screening is only one part of a bigger picture. "Internet companies present it as a single thing," he says. "They sell the Apo E4 gene and say it is the Alzheimer's gene." In fact, a whole series of genes and medical conditions (e.g. diabetes, hypertension, high cholesterol) have been tied to the memory-robbing condition. Detection of the ApoE4 allele, just like high cholesterol, hypertension or diabetes, should be seen as just another risk factor that may contribute to the risk, if left untreated.

Gknowmix is acutely conscious of trying to distinguish itself from less reputable companies: time and time again in my consultation I was reminded that genetic screening is only one part of my medical profile, and should be seen alongside my medical history, other medical tests, and lifestyle.

In 2006 a US Government Accountability Office (GAO) investigation found that genetic screening tests directly marketed to the public "mislead the consumer by making health-related predictions that are medically unproven and so ambiguous that they do not provide meaningful information to consumers".

Maritha Kotze, of Gknowmix and a geneticist at the University of Stellenbosch, emphasises that Gknowmix does not market their products directly to the public. Though tests can be requested through the Gknowmix website, Kotze explains that they cannot be processed without referral by a medical doctor or pre-test counselling by a registered genetic counsellor.

Jumping the gun
Much of the bad press is just a consequence of irresponsible companies abusing the lack of regulation in the industry. However, more serious questions are being asked about the actual science and clinical value of genetic screening.

A study published earlier this year in The American Journal of Human Genetics concluded that: "There is insufficient scientific evidence to conclude that genomic profiles are useful in measuring genetic risk for common diseases or in developing personalised diet and lifestyle recommendations for disease prevention."

It is a view shared by Helen Wallace, director of the UK-based organisation Gene Watch, who told us that "there is insufficient evidence for tailoring your diet to your genes except in some very specific circumstances".

And here lies at least part of the rub. While some genes are worth testing for, most may not be. That is partly why what Gknowmix is doing is different from what some overseas companies are doing – even though they function in the same field.

The last mile
Sceptics question the value of the tests. "Genetic tests for common genes related, for instance, to obesity or type 2 diabetes, are misleading because (i) further research has shown that many of these links are false; (ii) even where they have a genuine effect, it is very small compared to other factors; so the test is not useful for health," says Wallace.

Her views are echoed by two recent studies appearing in the New England Journal of Medicine which found that genetic screening for diabetes offers no benefit over traditional forms of screening and diagnosis.

Indeed, when it comes to real-world evidence that nutrigenetic screening is worthwhile, the evidence is lacking, particular with regard to specific dietary recommendations. To get back to the casino metaphor, though these tests can tell us what cards we're holding, we can't prove that we're playing better poker.

Hannes Viljoen, head of product and health risk management at Momentum Medical Scheme Administrators, says until there is more compelling evidence regarding the value of the tests, Momentum members will have to pay out of their savings accounts for nutrigenetic screening. "We do, however, follow the progress of this new field with great interest and will adapt our funding policy as the accuracy to customise treatment improves in relation to the cost of the tests," says Viljoen.

Strange bedfellows
Badenhorst believes nutrigenetic screening will eventually be driven by medical schemes, since such screening offers the potential to significantly reduce the burden of chronic lifestyle diseases.

Whether this promise will be fulfilled any time soon remains unclear.

What is happening, is that nutrigenetic screening is increasingly finding a home within the broader wellness movement, rather than the more stringently scientific medical world. This may have the effect of cementing the distrust some doctors feel toward it. Dr Kotze however believes that this can be changed through the "multi-disciplinary approach applied by Gknowmix and the laboratories involved with the testing."

Time to make some rules
Apart from more evidence, the future of nutrigenetic screening will depend to a large extent on the extent to which the industry is regulated. At the moment, for example, there is no regulatory oversight over Gknowmix's activities. And whereas it is my perception that they are taking a responsible approach, there is nothing stopping anyone from setting up another screening company in SA and exploiting consumers with false promises.

According to Wallace, Gene Watch wants to see regulation that involves an assessment of clinical validity (whether the gene is really linked to the claimed disease and, if so, how important it is) and utility (whether the test is really useful to decide whether to buy particular products or take particular advice) before a test is sold. Regulation is on the way only in the US; South Africa has no plans afoot.

All of this leaves one to conclude that apart from some exceptions (which your doctor may already know about) genetic screening, and nutrigenetic screening in particular, are still not ready for prime-time.

Apart from an odd existential glance into my genome, the test hasn't really made a difference to my life. What I saw was interesting, but much like a piece of modern art, its exact implications remains a bit murky.

I might try to rearrange my diet so as to get in a bit more folic acid; that's the kind of thing I was thinking about anyway. But then, as Kotze indicated, the test is meant for people with particular risk factors, and not for a relatively healthy person like myself.

- Marcus Low, Health24, November 2008

For more information you can phone Dr Maritha Kotze on 021 9389324 or registered genetic counsellor Julie Malan at 012 9974908 or email counselling@gknowmix.com.

The cost for a 1-hour counselling session is R 500 and the Wellness test (the one described in the article) costs R 2 950. DNA tests for cardiovascular disease and breast cancer are also available.

You can visit the Gknomix website at www.gknowmix.com and Molecular Diagnostic Services at www.mdsafrica.net.