A European study on the genetics of mite sensitization

Background: Sensitization to mite allergens represents a prominent feature of atopy and an important predictor of bronchial asthma. Objective: It was the intention of this study to define genetic loci linked to mite sensitization because these could represent the genetic basis of t he important atopic component of asthma. Methods: We studied a multiethnic white population of 99 families, includin g 224 sib pairs sensitized to Dermatophagoides pteronyssinus. A genome-wide candidate-region search was performed that covered potential asthma and at opy regions. Results: As for nonparametric linkage (NPL) analysis, 14 of the candidate r egions showed evidence for linkage (NPL > 2.0), and 4 of them showed promin ent linkage (NPL > 3.0). However, there were substantial ethnic differences . Maximizing the LOD score analysis identified candidate regions with suspe cted dominant and recessive mode of inheritance. Furthermore, genetic impri nting models provided significant evidence for linkage in the 8p23 region a nd revealed potential maternal imprinting. The regions found are distinct t o those in asthma searches that have been found to be linked to asthma, as well to other inflammatory diseases. In addition, we could not Find linkage to the HLA region. By different cutoff points of the phenotype definition, the IL cluster showed evidence of being linked to the degree of sensitizat ion rather than to sensitization per se. Conclusion: The results indicate that the genetic basis of the atopic compo nent of asthma is different from that of the inflammatory component. Furthe rmore, it seems reasonable to assume that specific sensitizations are influ enced by distinct genetic variants leading to their initiation versus those leading to their enhancement.