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

Nobuyuki Hizawa, Gary Collins, Thorunn Rafnar, Shau Ku Huang, David L. Duffy, James L. Weber, Linda R. Freidhoff, Eva Ehrlich, David G. Marsh, Terri H. Beaty, Kathleen C. Barnes

Research output: Contribution to journalArticle

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Abstract

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)443-448
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume102
Issue number3
DOIs
Publication statusPublished - Jan 1 1998
Externally publishedYes

Fingerprint

HLA-D Antigens
Dermatophagoides pteronyssinus
Genetic Markers
Immunoglobulin E
Peptides
Alleles
Antibodies
Immunoblotting
Asthma
Genes
Dermatophagoides Antigens
Immunoassay
Chromosomes
Parents
Genome

Keywords

  • Dermatophagoides pteronyssinus-specific IgE responsiveness
  • HLA-D genes
  • Immunoblotting analysis
  • Transmission/disequilibrium test

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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. / Hizawa, Nobuyuki; Collins, Gary; Rafnar, Thorunn; Huang, Shau Ku; Duffy, David L.; Weber, James L.; Freidhoff, Linda R.; Ehrlich, Eva; Marsh, David G.; Beaty, Terri H.; Barnes, Kathleen C.

In: Journal of Allergy and Clinical Immunology, Vol. 102, No. 3, 01.01.1998, p. 443-448.

Research output: Contribution to journalArticle

Hizawa, Nobuyuki ; Collins, Gary ; Rafnar, Thorunn ; Huang, Shau Ku ; Duffy, David L. ; Weber, James L. ; Freidhoff, Linda R. ; Ehrlich, Eva ; Marsh, David G. ; Beaty, Terri H. ; Barnes, Kathleen C. / 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. In: Journal of Allergy and Clinical Immunology. 1998 ; Vol. 102, No. 3. pp. 443-448.
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abstract = "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. Conclusion: 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.",
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AU - Collins, Gary

AU - Rafnar, Thorunn

AU - Huang, Shau Ku

AU - Duffy, David L.

AU - Weber, James L.

AU - Freidhoff, Linda R.

AU - Ehrlich, Eva

AU - Marsh, David G.

AU - Beaty, Terri H.

AU - Barnes, Kathleen C.

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