GENETIC-REGULATION OF DERMATOPHAGOIDES PTERONYSSINUS-SPECIFIC IGE RESPONSIVENESS - A GENOME-WIDE MULTIPOINT LINKAGE ANALYSIS IN FAMILIES RECRUITED THROUGH 2 ASTHMATIC SIBS

Background: Dermatophagoides pteronyssinus (Der p) is one of the most frequently implicated allergens in atopic diseases. Although HLA could play an important role in the development of the IgE response to the Der p allergens, genetic regulation by non-HLA genes influences certai n HLA-associated IgE responses to complex allergens. Objective: To cla rify genetic control for the expression of Der p-specific IgE, respons iveness, we conducted a genome-wide search for genes influencing Der p -specific IgE antibody levels by using 45 Caucasian and 53 African Ame rican families ascertained as part of the Collaborative Study on tho G enetics of Asthma (CSGA). Methods: Specific IgE antibody levels to the Der p crude allergen and to the purified allergens Der p 1 and Der p 2 were measured. Multipoint, nonparametric linkage analysis of 370 pol ymorphic markers was performed with the GENE-HUNTER program. Results: The best evidence of genes controlling specific IgE response to Der p was obtained in 2 novel regions: chromosomes 2q21-q23 (P =.0033 for Ca ucasian subjects) and 8p23-p21 (P =.0011 for African American subjects ). Three regions previously proposed as candidate regions for atopy, t otal IgE, or asthma also showed evidence for linkage to Der p-specific IgE responsiveness: 6p21 (P =.0064) and 13q32-q34 (P = 0.0064) in Cau casian subjects and 5q23-q33 (P = 0.0071) in African American subjects . Conclusions: No single locus generated overwhelming evidence for lin kage in terms of established criteria and guidelines for a genome-wide screening, which supports previous assertions of a heterogeneous etio logy for Der p-specific IgE responsiveness. Two novel regions, 2q21-q2 3 and 8p23-p21, that were identified in this study merit additional st udy.