LINKAGE ANALYSIS OF DERMATOPHAGOIDES PTERONYSSINUS-SPECIFIC IGE RESPONSIVENESS WITH POLYMORPHIC MARKERS ON CHROMOSOME 6P21 (HLA-D REGION) IN CAUCASIAN FAMILIES BY THE TRANSMISSION DISEQUILIBRIUM TEST/

Background: Recently, we have obtained evidence for linkage between De r p 1-specific IgE antibodies and markers on chromosome 6p21 (HLA-D re gion) in a genome-wide screening in Caucasian families recruited as a part of the Collaborative Study on the Genetics of Asthma (CSGA). Obje ctive: Specific IgE antibodies toward different Dermatophagoides ptero nyssinus (Der p) polypeptides were detected by immunoblotting analysis , and the transmission/disequilibrium test (TDT) was performed between specific IgE responsiveness toward each different Der p polypeptide a nd markers on chromosome 6p21 to better clarify the genetic contributi on of HLA-D genes. Methods: We studied 299 individuals in 45 Caucasian families participating in the CSGA. Serum samples from 137 individual s that showed elevated specific IgE antibodies toward the Der p crude allergen (> -0.5 log IU/mL) by ACCESS immunoassay were subjected to im munoblotting analysis. TDT was conducted between the presence of speci fic IgE antibodies toward each of It different Der p polypeptides and 4 polymorphic markers on chromosome 6p21. Results: The 196-bp allele o f D6S1281 and the 104-bp allele of DQCAR showed significant excess tra nsmission to specific IgE responders toward a particular Der p polypep tide (120 kd, 55 kd, 45 kd, or 37 kd), In contrast, the 200-bp allele of D6S1281 and the 204-bp allele of D6S291 showed significantly decrea sed transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 90 kd, 52 kd, or 45 kd). Deviation from the expec ted 50% transmission in heterozygous parents was statistically signifi cant after correcting for multiple comparisons. Conclusion: This study supported our previous findings that genes on chromosome 6p21 (HLA-D region) may influence the expression of Der p-specific IgE responsiven ess in this Caucasian population. Our results, however, reveal the com plexity of genetic regulations of Der p-specific IgE responsiveness by HLA-D genes, suggesting the strong influence of non-HLA loci and perh aps environmental factors for the development of Der p-specific IgE re sponsiveness.