The new asthma genetics and its implications for public health.

OBJECTIVE

To review the genetics of asthma from a public health perspective.

DATA SOURCES

Studies of asthma genetics published between 1990 and 1997 were reviewed.

STUDY SELECTION

Studies based on random population sampling were preferred. Both linkage and association studies were included, as were genome scans. Studies needed to report results for asthma or the related traits of atopy and bronchial hyperreactivity (BHR).

DATA EXTRACTION

The chromosomal locations linked to or candidate genes associated with asthmatic traits were tabulated.

DATA SYNTHESIS

A clear majority of studies relied on clinical ascertainment or highly inbred populations. Although there is no consensus about the definition of asthma, phenotypic characterisation of subjects is more complete in recent studies. The high affinity IgE receptor gene on chromosome 11q and a cluster of cytokine genes on chromosome 5q are linked both to atopy and BHR. The T cell receptor gene on chromosome 14q is linked to specific IgE responses, and a region on chromosome 12q is linked both to total IgE levels and asthma. Genome scans have identified other regions of interest on chromosomes 2q, 4, 5p, 6, 7, 11p, 13, 16, 17, 19q, and 21q.

CONCLUSIONS

Asthma is a complex polygenic disorder with marked gene-environment interactions. However, it is proving tractable to powerful new genetic approaches arising from the human genome project. At the present state of knowledge, population screening for the asthma genes so far identified cannot be justified. Gene therapy for asthma is an even more remote prospect.