The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype is a risk factor for toluene diisocyanate-induced occupational asthma

Jeong Hee Choi, Kyung Wha Lee, Cheol Woo Kim, Choon Sik Park, Hyun Young Lee, Gyu Young Hur, Seung Hyun Kim, Chein Soo Hong, An Soo Jang, Hae Sim Park

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. Methods: Patients with TDI-OA (n = 84), asymptomatic exposed controls (AECs, n = 47) and unexposed normal controls (NCs, n = 127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. Results: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602- DPB1*0501 haplotype was significantly higher in TDI-OA patients (19%) than in AEC (2.1%, p = 0.007, OR 4.429, CI 1.497-13.103) or NC (3.1%, p < 0.001, OR 7.235, CI 2.236-22.510) subjects, with statistical significance persisting after correction for multiple comparisons. DQB1*0402 was significantly associated with the presence of specific IgE to TDI-albumin conjugates in serum (p = 0.006, OR 4.552, CI 1.540-13.449). This p value remained significant after correction for multiple comparison. Conclusion: The HLA DRB1*1501-DQB1 *0602-DPB1* 0501 haplotype may be a genetic marker for the development of TDI-induced asthma in Koreans. Several HLA alleles that enhance specific IgE sensitization in exposed subjects are indicated.

Original languageEnglish
Pages (from-to)156-163
Number of pages8
JournalInternational Archives of Allergy and Immunology
Volume150
Issue number2
DOIs
Publication statusPublished - 2009 Sep 1

Fingerprint

Toluene 2,4-Diisocyanate
Occupational Asthma
HLA Antigens
Haplotypes
Immunoglobulin E
Asthma
Albumins
Alleles
HLA-DQB1 antigen
Serum
DNA Sequence Analysis
Genetic Markers
Gene Frequency
Enzyme-Linked Immunosorbent Assay

Keywords

  • Asthma
  • Human leukocyte antigen class
  • Immunoglobulin E
  • Toluene diisocyanate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype is a risk factor for toluene diisocyanate-induced occupational asthma. / Choi, Jeong Hee; Lee, Kyung Wha; Kim, Cheol Woo; Park, Choon Sik; Lee, Hyun Young; Hur, Gyu Young; Kim, Seung Hyun; Hong, Chein Soo; Jang, An Soo; Park, Hae Sim.

In: International Archives of Allergy and Immunology, Vol. 150, No. 2, 01.09.2009, p. 156-163.

Research output: Contribution to journalArticle

Choi, Jeong Hee ; Lee, Kyung Wha ; Kim, Cheol Woo ; Park, Choon Sik ; Lee, Hyun Young ; Hur, Gyu Young ; Kim, Seung Hyun ; Hong, Chein Soo ; Jang, An Soo ; Park, Hae Sim. / The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype is a risk factor for toluene diisocyanate-induced occupational asthma. In: International Archives of Allergy and Immunology. 2009 ; Vol. 150, No. 2. pp. 156-163.
@article{24d3be8658724fecb762c44410d5b233,
title = "The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype is a risk factor for toluene diisocyanate-induced occupational asthma",
abstract = "Background: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. Methods: Patients with TDI-OA (n = 84), asymptomatic exposed controls (AECs, n = 47) and unexposed normal controls (NCs, n = 127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. Results: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602- DPB1*0501 haplotype was significantly higher in TDI-OA patients (19{\%}) than in AEC (2.1{\%}, p = 0.007, OR 4.429, CI 1.497-13.103) or NC (3.1{\%}, p < 0.001, OR 7.235, CI 2.236-22.510) subjects, with statistical significance persisting after correction for multiple comparisons. DQB1*0402 was significantly associated with the presence of specific IgE to TDI-albumin conjugates in serum (p = 0.006, OR 4.552, CI 1.540-13.449). This p value remained significant after correction for multiple comparison. Conclusion: The HLA DRB1*1501-DQB1 *0602-DPB1* 0501 haplotype may be a genetic marker for the development of TDI-induced asthma in Koreans. Several HLA alleles that enhance specific IgE sensitization in exposed subjects are indicated.",
keywords = "Asthma, Human leukocyte antigen class, Immunoglobulin E, Toluene diisocyanate",
author = "Choi, {Jeong Hee} and Lee, {Kyung Wha} and Kim, {Cheol Woo} and Park, {Choon Sik} and Lee, {Hyun Young} and Hur, {Gyu Young} and Kim, {Seung Hyun} and Hong, {Chein Soo} and Jang, {An Soo} and Park, {Hae Sim}",
year = "2009",
month = "9",
day = "1",
doi = "10.1159/000218118",
language = "English",
volume = "150",
pages = "156--163",
journal = "International Archives of Allergy and Immunology",
issn = "1018-2438",
publisher = "S. Karger AG",
number = "2",

}

TY - JOUR

T1 - The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype is a risk factor for toluene diisocyanate-induced occupational asthma

AU - Choi, Jeong Hee

AU - Lee, Kyung Wha

AU - Kim, Cheol Woo

AU - Park, Choon Sik

AU - Lee, Hyun Young

AU - Hur, Gyu Young

AU - Kim, Seung Hyun

AU - Hong, Chein Soo

AU - Jang, An Soo

AU - Park, Hae Sim

PY - 2009/9/1

Y1 - 2009/9/1

N2 - Background: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. Methods: Patients with TDI-OA (n = 84), asymptomatic exposed controls (AECs, n = 47) and unexposed normal controls (NCs, n = 127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. Results: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602- DPB1*0501 haplotype was significantly higher in TDI-OA patients (19%) than in AEC (2.1%, p = 0.007, OR 4.429, CI 1.497-13.103) or NC (3.1%, p < 0.001, OR 7.235, CI 2.236-22.510) subjects, with statistical significance persisting after correction for multiple comparisons. DQB1*0402 was significantly associated with the presence of specific IgE to TDI-albumin conjugates in serum (p = 0.006, OR 4.552, CI 1.540-13.449). This p value remained significant after correction for multiple comparison. Conclusion: The HLA DRB1*1501-DQB1 *0602-DPB1* 0501 haplotype may be a genetic marker for the development of TDI-induced asthma in Koreans. Several HLA alleles that enhance specific IgE sensitization in exposed subjects are indicated.

AB - Background: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. Methods: Patients with TDI-OA (n = 84), asymptomatic exposed controls (AECs, n = 47) and unexposed normal controls (NCs, n = 127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. Results: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602- DPB1*0501 haplotype was significantly higher in TDI-OA patients (19%) than in AEC (2.1%, p = 0.007, OR 4.429, CI 1.497-13.103) or NC (3.1%, p < 0.001, OR 7.235, CI 2.236-22.510) subjects, with statistical significance persisting after correction for multiple comparisons. DQB1*0402 was significantly associated with the presence of specific IgE to TDI-albumin conjugates in serum (p = 0.006, OR 4.552, CI 1.540-13.449). This p value remained significant after correction for multiple comparison. Conclusion: The HLA DRB1*1501-DQB1 *0602-DPB1* 0501 haplotype may be a genetic marker for the development of TDI-induced asthma in Koreans. Several HLA alleles that enhance specific IgE sensitization in exposed subjects are indicated.

KW - Asthma

KW - Human leukocyte antigen class

KW - Immunoglobulin E

KW - Toluene diisocyanate

UR - http://www.scopus.com/inward/record.url?scp=65549113060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549113060&partnerID=8YFLogxK

U2 - 10.1159/000218118

DO - 10.1159/000218118

M3 - Article

C2 - 19439981

AN - SCOPUS:65549113060

VL - 150

SP - 156

EP - 163

JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

SN - 1018-2438

IS - 2

ER -