Contributing factors to the pathobiology. The genetics of asthma.

Markers in 19 chromosomal regions have shown some evidence of linkage to asthma, atopy, or related phenotypes in multiple independent genome-wide searches. Linkages to five of these regions (5q, 6p, 11q, 12q, and 13q) have also been reported in non-genome-wide screens. In addition, at least two independent studies have reported linkages to markers on 16p. Numerous candidate genes in these regions have shown varying levels of association to asthma or atopic phenotypes, potentially implicating them as disease susceptibility loci. These include the IL4, CD14, and B2ADR genes on 5q, the HLA-DRB1 and TNF genes on 6p, the FCERB1 and CC16 genes on 11q, and the IL4RA gene on 16p. It still remains to be determined whether polymorphisms in these genes account for the reported linkages in these regions. Studies are underway in laboratories around the world to identify the disease-causing variations in these genes that account for the linkages just discussed. Identifying specific genetic polymorphisms that influence asthma and atopic phenotypes will shed light on the molecular pathways involved in these complex disorders and provide a better understanding of the pathophysiology of asthma and atopy.