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Can I have psoriasis in my genes?

 

Twenty five percent of people with psoriasis suffer from a genetically inherited form of the condition. However, there is no "psoriasis gene". Instead, there are several genes that cause a predisposition towards psoriasis, located in various chromosomal regions. This section deals with the role of genetics in psoriasis.

 

Introduction

 

Psoriasis is a chronic, multifactorial skin condition, whose causes may be genetic, immunological, environmental and psychological. These factors alter the functioning of skin cells, in particular that of keratinocytes and fibroblasts. Doctors distinguish between type 1 and type 2 psoriasis. In type 1, the condition appears in a child or young adult with a family history of psoriasis. This condition tends to develop quite severely. Type 2 psoriasis appears in people who are over 40 and there is a weaker influence of family history (1). This condition typically develops less severely.

 

Psoriasis results from a genetic predisposition in at least 25% of cases. This genetic susceptibility was first demonstrated in the 1960's by studies on the population of the Faroe Islands, off the coast of northern Europe. However, there is no single "psoriasis gene". Instead, a cluster of genes cause the skin to over-react to certain stimuli, such as infectious diseases, stress and climatic factors.

 

All skin reacts to environmental factors, and normal skin renewal is accelerated by physical stress and friction. However, in people with psoriasis, environmental aggravations cause such a strong reaction that the skin begins to peel, leading to inflammation. It is this continued inflammation that makes the condition chronic.

 

The current knowledge of the genes associated with psoriasis is incomplete. However, a study of the families of people with psoriasis has demonstrated that there are chromosomal regions associated with the condition. In the near future, scientists hope to identify the genes involved in psoriasis, which will help us to understand the mechanisms involved in the condition.

 

A complex genetic disorder

 

Research* on monozygotic twins (i.e. identical twins who have the same genetic setup) showed that when one twin suffered from psoriasis, there was a 65% to 72% probability that the other twin would also have the condition. In dizygotic twins (non-identical twins), this probability was between 15% and 30% (2) .

 

These figures show that genetics are involved in psoriasis, but they also demonstrate that hereditary factors are not the only cause. If they were, there would be a 100% probability in the case of identical twins. As a result, it is clear that psoriasis is also influenced by environmental factors. At the moment, the number and nature of genetic and environmental factors involved in the onset of psoriasis are unknown.

 

Moreover, the prevalence varies between populations. In France, 3% of the population is affected by psoriasis. However, in certain northern European countries (such as Sweden and Finland) and Russia, 6% to 8% of the population has the condition. Native Americans from the Andes and Eskimos do not seem to get psoriasis. This can possibly be explained by genetic differences coupled with environmental factors. 

 

The HLA system and its key role in immunity

 

From a clinical point of view, psoriasis is the consequence of an abnormal proliferation of skin cells, lymphocytic infiltration and vasodilatation. Chronic inflammation of the skin also occurs, caused by polymorphonuclear neutrophils and T lymphocytes. As the latter also play a key role in the immune response, it becomes apparent that the immune system is involved to a large extent in psoriasis.

 

It has been suggested that psoriasis is an autoimmune disease, like rheumatoid polyarthritis or ankylosing spondylitis. The function of the immune system is to protect us from external attack by viruses, bacteria, parasites and so on. However, in a person with an autoimmune disorder, the immune system attacks parts of the host organism as well foreign bodies. Psoriasis may be either a skin condition or an immune disorder which presents with skin manifestations. An increasing amount of evidence supports the second hypothesis. However, it remains controversial whether psoriasis can be classified as a true autoimmune disorder (3).

 

The HLA (Human Leukocyte Antigen) system which is found on the short arm of chromosome 6 is at the heart of the immune system. It consists of antigens which are present on the surface of all cells in our bodies. These antigens involve five genes, and they are particularly involved in recognising and responding to external antigens. They capture antigenic material (e.g. bacterial debris) and present it into the body in order to prepare the immune system for a recurrence of the same external attack. The HLA system consists of numerous sub-units, which leads to an astonishing variety. Each of us has an individual HLA system, and it is this system which is important in transplantation immunity. When a transplantation is performed, the donor and the recipient must be HLA compatible in order for the transplant to be accepted by the recipient's immune system (3).

 

Several genes are involved in psoriasis

 

A number of studies emphasise that the HLA systems of people with psoriasis have a shared characteristic: 66% of the patients have a specific variation in the HLA region on chromosome 6 (HLA Cw6). There is a specific genetic constellation known as Cw6, which is present on the C gene of chromosome 6. Whilst this is not a genetic abnormality, it is a risk factor associated with psoriasis. It is comparable to the fact that skin which is sensitive to UV rays is more typical of redheads than brunettes. The HLA Cw6 gene which is present in psoriasis patients has not undergone mutation. Just carrying the gene does not mean that the carrier will develop psoriasis. In fact, 10% of the overall population carries HLA Cw6 and not all of them have psoriasis. Conversely, there are people with psoriasis who do not carry this gene.

 

All of this information serves to illustrate the complex nature of psoriasis. It also explains why scientists consider that different types of psoriasis (such as plaque psoriasis, pustular psoriasis and psoriatic arthritis) are in fact distinct conditions, with different genetic factors involved in each clinical form. In support of this hypothesis the condition can appear at various ages and there is much diversity in the course of the disease (some patients only experience one flare, whereas others have to live with the condition for their whole lives).

 

Numerous scientific studies from around the world show that other genes are involved in psoriasis. The HLA system is only one piece of the puzzle. "Research is advancing slowly because contrary to appearances, we do not really understand the immune system," says Dr Jean-François Prud'homme from Généthon. "Although thanks to technology we can identify individual factors, we are less capable when it comes to more complex systems. But we will be more effective in the future." It is thought that less than ten genes are involved as one patient in four has genetically inherited psoriasis. If numerous genes were involved, the probability of transmitting the condition would be lower.

 

 

References:

1) Swanbeck et al., Br J Dermatol, 1995.

2) Schon, N Engl J Med, 2005.

3) Bowcock & Krueger, Nat Rev Immunol, 2005.

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