Gene Defect Linked To Allergy, BMJ Finds

Defects in a particular gene - the filaggrin gene - are associated with a significantly increased risk of developing allergic disorders such as eczema, rhinitis, and asthma, concludes a study published on bmj.com today.

Allergic diseases have increased in recent decades and now affect up to one in three children in economically developed countries. For many years researchers have looked for genes that might contribute to allergic diseases but, until recently no major associations had been described, and a real "allergy gene" was elusive.

However, recent reports have consistently pointed to a strong influence of the filaggrin gene in maintaining an effective skin barrier against the environment.

So researchers at the University of Edinburgh analysed the results of 24 studies to investigate if filaggrin gene mutations increase the risk of developing allergic sensitisation and allergic disorders.

Differences in study quality were taken into account to identify and minimise bias.

Pooling the results showed that filaggrin gene mutations significantly increase the risk of developing allergic sensitisation, atopic eczema, allergic rhinitis, and asthma in people with eczema. The relationship between filaggrin gene mutations and atopic eczema was particularly strong.

Filaggrin gene mutations also increased the risk of asthma in people with atopic eczema.

"These findings provide strong supporting evidence that, at least in a subset of those with allergic problems, the filaggrin gene defect may be the fundamental predisposing factor not only for the development of eczema but also for initial sensitisation and progression of allergic disease," said the authors.

"Our finding suggest that filaggrin is a robust biomarker for allergic conditions," they add.

Further studies now need to explore whether filaggrin can be used to identify those at high risk. Restoring skin barrier function in filaggrin deficient people in early life may also help prevent the development of sensitisation and halt the development and progression of allergic disease, they conclude.

This study represents an important breakthrough in understanding the genetic basis of this complex disorder, said experts from Singapore in an accompanying editorial. The next challenge will be to distinguish different genotypes of allergy, which could revolutionise the prevention, diagnosis, and treatment of allergy in children, they conclude.

(JM/BMcc)