Allergies and Inheritance. WHY ALLERGY RUNS IN FAMILIES
Allergies and
inheritance
WHY IT RUNS IN
FAMILIES
`My father had asthma as a child, and his sister had it too. In fact she died from it. My mother has never had any allergies, but one of her brothers had terrible hayfever all his life. Out of us four, only my brother Peter is completely allergy-free. I had bad eczema when I was small, as did my sister. So when our son developed eczema, and then asthma, and an allergy to house-dust mite which made his nose run all the time, I wasn’t entirely surprised.’ What Janet’ is describing is a good example of an atopic family — one where classical allergies, of one kind or another, affect several family members. The members of such a family are called atopics.
Atopics have an underlying tendency to allergy which, with luck, may never be expressed. But if they are unlucky, the tendency will lead to allergies, which can settle on the skin (atopic eczema), the nose (hayfever or perennial allergic rhinitis), the airways (asthma) or the mouth and digestive tract (food allergy). These diseases, which recur down the generations in atopic families like Janey’s, are known as the classical allergic diseases.
The atopic tendency is coded into our DNA –in the genes that are passed from parent to child. There are also other genes that make asthma more likely to develop, and these can work in concert with the allergy-promoting genes to produce asthma in a child. And there are probably genes for dry skin, which contribute to atopic eczema.
Genes alone are not enough, however. Environment (which means, in medical terms, everything external that affects an individual,
including diseases, diet, air, allergens such as dust mite or pollen, and even medical treatment) also plays a large part in promoting allergic reactions. In other words, genes and the external world interact to produce allergic disease. What happens in the months and years immediately after birth seems to be a crucial element.
This helps to explain why allergies are on the increase even though we are, genetically speaking, not so different from our grandparents or great-grandparents. It is also a cause for optimism, since it means we can largely reverse the trend in coming generations. All we have to do is adjust the environment, especially for newborns and young children. Luckily, most of the problem factors are ones over which we have personal control, such as smoking by parents, diet, infant feeding, hygiene (less is better), antibiotic treatment, house design and furnishings Generally speaking, inherited traits such as height or skin colour are governed, not by a single gene with a large effect, but by a great many genes each with a small effect. This is called multi-gene inheritance. The many small effects add up to produce the final outcome. Atopy is probably inherited in a similar way, which would explain why some people have a very strong tendency to allergies (they have lots of the wrong genes) while other people have only a mild tendency (they have just a few).
Current estimates hold that at least twenty different genes are involved in determining atopy. This means that no two atopic individuals are going to be quite the same, because each will have a different combination of the possible variants on these twenty genes. In the words of Dr Vincent Beltrani, of Columbia University, New York, ‘it is not surprising that, as a result of all the possible genetic combinations and permutations, each atopic individual possesses a unique “allergic fingerprint” and that not all atopic individuals have identical findings’.
Multi-gene inheritance has another important effect, in terms of predicting who will develop allergies. The genetic risks from the two parents add up, so if both parents have allergies themselves or come from atopic families, the risks of the child developing allergies are much higher than if only one parent is atopic. The actual figures are uncertain because the results vary considerably from one study to another. If one parent is atopic, the risk can range from 20% to 58%, whereas if both parents are atopic, the risk ranges from 50% to 80% or even more.
Note that these are just risks: there are no certainties here because the actual mix of genes that a child receives is a selection – half of the mother’s genes and half of the father’s. There’s no saying which half a child gets, because this is a random selection process, similar to the shuffling and dealing of playing cards. Luck plays a big part.
Naturally enough, both atopic parents and their doctors have asked whether there is any test that could assess the number of pro-allergy genes in a newborn and so predict the chances of allergy developing in particular children. That would allow more stringent anti-allergy measures to be taken for the children most at risk.
Various tests have been tried, and one does work, to a limited extent. It involves measuring the level of the allergy antibody, IgE, in a blood sample taken from the umbilical cord just after birth. Very high levels of IgE give some indication of the chances of allergies developing later, but the accuracy of the prediction is, unfortunately, not that good when the test is carried out in atopic families. The test doesn’t reveal much more than is already known – that the baby has atopic parents.
This same test, when carried out on newborns who are not from atopic families, sometimes gives a much more useful and accurate result. In one study, 75% of those babies with high levels of cord-blood IgE developed allergies a few years later, compared to only 6% of those with low levels. Unfortunately, the test does not always give such impressive results, and some disappointing studies have led doctors to conclude that it is not worthwhile as a standard test for all newborns.
This finding of high IgE in children from non-atopic families highlights an important point: pro-allergy genes are everywhere. A lot of healthy people have them, but at levels which do not cause any symptoms – yet. This explains why, with the allergy epidemic, many new allergy sufferers are coming from families never affected by allergy before. As our lifestyle becomes more pro-allergy, a baby needs fewer of the pro-allergy genes to grow into an allergic individual.
Other forms of sensitivity
The multi-gene inheritance of classical allergy is very different from the inheritance of diseases such as primary lactase deficiency where there is a single gene that is at fault. Generally, speaking, all metabolic abnormalities are inherited in this straightforward way, so they are an all-or-nothing affair: one child in the family gets the defective gene while another does not. No environmental triggers are needed to activate the defect.
In the case of food intolerance, if minor metabolic abnormalities play a part, as they may do for some sufferers, then there could be inheritance of the defect, but this will not necessarily lead to symptoms unless other intolerance-promoting factors (such as disturbed gut flora) are present. Those who suffer from both food intolerance and chemical intolerance (also called chemical sensitivity) are the most likely to have metabolic abnormalities, and it is interesting that such problems do sometimes affect several members of the same family. (Doctors who are sceptical about such diseases will dismiss this as simply ‘learned illness behaviour’ among family members, a theory that is difficult to test without a lot of expensive research.)
Inheritance plays a part in several other forms of sensitivity. It is very important, for example, in coeliac disease and dermatitis herpetiformis , which both stem from the same genetic feature. They are only expressed when wheat is eaten but the timing is important here – introducing wheat into a child’s diet later, rather than during the first year of life, seems less likely to provoke the disease. When coeliac disease comes on in adult life, it suggests that some other environmental trigger was needed, in addition to eating wheat, to start off the disease process.