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. Collaborative Study on the Genetics of Asthma (CSGA).
BACKGROUND
Recently, we have obtained evidence for linkage between Der p 1-specific IgE antibodies and markers on chromosome 6p21 (HLA-D region) in a genome-wide screening in Caucasian families recruited as a part of the Collaborative Study on the Genetics of Asthma (CSGA).


OBJECTIVE
Specific IgE antibodies toward different Dermatophagoides pteronyssinus (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 and markers on chromosome 6p21 to better clarify the genetic contribution of HLA-D genes.


METHODS
We studied 299 individuals in 45 Caucasian families participating in the CSGA. Serum samples from 137 individuals that showed elevated specific IgE antibodies toward the Der p crude allergen (> -0.5 log IU/mL) by ACCESS immunoassay were subjected to immunoblotting analysis. TDT was conducted between the presence of specific IgE antibodies toward each of 12 different Der p polypeptides and 4 polymorphic markers on chromosome 6p21.


RESULTS
The 196-bp allele of D6S1281 and the 104-bp allele of DQCAR showed significant excess transmission to specific IgE responders toward a particular Der p polypeptide (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 decreased transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 90 kd, 52 kd, or 45 kd). Deviation from the expected 50% transmission in heterozygous parents was statistically significant after correcting for multiple comparisons.


CONCLUSIONS
This study supported our previous findings that genes on chromosome 6p21 (HLA-D region) may influence the expression of Der p-specific IgE responsiveness in this Caucasian population. Our results, however, reveal the complexity of genetic regulations of Der p-specific IgE responsiveness by HLA-D genes, suggesting the strong influence of non-HLA loci and perhaps environmental factors for the development of Der p-specific IgE responsiveness.
Division of Clinical Immunology, The Johns Hopkins Asthma & Allergy Center, Baltimore, MD 21224, USA.
N
N
Hizawa
G
G
Collins
T
T
Rafnar
S K
SK
Huang
D L
DL
Duffy
J L
JL
Weber
L R
LR
Freidhoff
E
E
Ehrlich
D G
DG
Marsh
T H
TH
Beaty
K C
KC
Barnes
D000483:Alleles; D000818:Animals; D000918:Antibody Specificity; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006023:Glycoproteins / Q000276:immunology*; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000235:genetics* / Q000276:immunology*; D015810:Linkage Disequilibrium; D008297:Male; D008925:Mites / Q000276:immunology*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D006681:HLA-D Antigens; D007073:Immunoglobulin E