Transracial evidence for the influence of the homologous HLA DR-DQ haplotype on transmission of HLA DR4 haplotypes to diabetic children

Y. S. Park, Jin-Xiong She, J. A. Noble, H. A. Erlich, G. S. Eisenbarth

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The HLA-DQB1*0302 allele on DR4 haplotypes is a marker for type 1 diabetes susceptibility and it is an especially high-risk allele in DR3/4 because of its preferential distribution in Caucasian DR3/4 patients. In Asians, not only DQB1*0302 but also DQB1*0401 on DR4 haplotypes are associated with type 1 diabetes. We investigated whether the contribution of these DQ molecules was also genotype-dependent in Asians. Although the prevalence of the DR4-DQB1*0302 haplotype did not differ in patients vs. controls, the DR3/4-DQB1*0302 genotype had a RR of 12 (P<10-4). Moreover, a significant association of DQB1*0302 with the DR3/4 genotype was found (RR=3, P<10-2). In contrast, the distribution of DQB1*0401 alleles of DR4/X (X: other than 3, 4) is different from that of DR3/4 and DR4/4. Especially a significant association of DQB1*0401 with DR4/X (X: other than 1, 3, 4) was found (RR=3, P<10-3). The frequency of transmission of the DR4-DQB1*0302 haplotypes to diabetic offspring with DR3 was 80%, while to those without DR3 was 40%. In contrast, the transmission of the DR4-DQB1*0401 to those with DR3 was 60%, while to those without DR3 was 80%. High-risk DR4 subtypes were predominant in DR4/X (RR=7, P<10-3), whereas protective DR4 subtypes were observed mainly in the DR3/4 (RR=3, P<0.05). The association with diabetes and transmission to a diabetic offspring of DR4 haplotypes varies depending on the haplotype borne on the homologous chromosome. This might contribute not only to the synergistic effect of DR3/4, but also to the susceptibility influence of HLA DQB1*0401 alleles confined to DR4/X.

Original languageEnglish (US)
Pages (from-to)185-191
Number of pages7
JournalTissue Antigens
Volume57
Issue number3
DOIs
StatePublished - Apr 11 2001
Externally publishedYes

Fingerprint

HLA-DR4 Antigen
HLA-DQ Antigens
HLA-DR Antigens
Haplotypes
Alleles
Genotype
Type 1 Diabetes Mellitus
Chromosomes

Keywords

  • Association
  • DQB1*0401
  • Genetic susceptibility
  • HLA DQB1*0302
  • Transmission
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Genetics

Cite this

Transracial evidence for the influence of the homologous HLA DR-DQ haplotype on transmission of HLA DR4 haplotypes to diabetic children. / Park, Y. S.; She, Jin-Xiong; Noble, J. A.; Erlich, H. A.; Eisenbarth, G. S.

In: Tissue Antigens, Vol. 57, No. 3, 11.04.2001, p. 185-191.

Research output: Contribution to journalArticle

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abstract = "The HLA-DQB1*0302 allele on DR4 haplotypes is a marker for type 1 diabetes susceptibility and it is an especially high-risk allele in DR3/4 because of its preferential distribution in Caucasian DR3/4 patients. In Asians, not only DQB1*0302 but also DQB1*0401 on DR4 haplotypes are associated with type 1 diabetes. We investigated whether the contribution of these DQ molecules was also genotype-dependent in Asians. Although the prevalence of the DR4-DQB1*0302 haplotype did not differ in patients vs. controls, the DR3/4-DQB1*0302 genotype had a RR of 12 (P<10-4). Moreover, a significant association of DQB1*0302 with the DR3/4 genotype was found (RR=3, P<10-2). In contrast, the distribution of DQB1*0401 alleles of DR4/X (X: other than 3, 4) is different from that of DR3/4 and DR4/4. Especially a significant association of DQB1*0401 with DR4/X (X: other than 1, 3, 4) was found (RR=3, P<10-3). The frequency of transmission of the DR4-DQB1*0302 haplotypes to diabetic offspring with DR3 was 80{\%}, while to those without DR3 was 40{\%}. In contrast, the transmission of the DR4-DQB1*0401 to those with DR3 was 60{\%}, while to those without DR3 was 80{\%}. High-risk DR4 subtypes were predominant in DR4/X (RR=7, P<10-3), whereas protective DR4 subtypes were observed mainly in the DR3/4 (RR=3, P<0.05). The association with diabetes and transmission to a diabetic offspring of DR4 haplotypes varies depending on the haplotype borne on the homologous chromosome. This might contribute not only to the synergistic effect of DR3/4, but also to the susceptibility influence of HLA DQB1*0401 alleles confined to DR4/X.",
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AU - She, Jin-Xiong

AU - Noble, J. A.

AU - Erlich, H. A.

AU - Eisenbarth, G. S.

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AB - The HLA-DQB1*0302 allele on DR4 haplotypes is a marker for type 1 diabetes susceptibility and it is an especially high-risk allele in DR3/4 because of its preferential distribution in Caucasian DR3/4 patients. In Asians, not only DQB1*0302 but also DQB1*0401 on DR4 haplotypes are associated with type 1 diabetes. We investigated whether the contribution of these DQ molecules was also genotype-dependent in Asians. Although the prevalence of the DR4-DQB1*0302 haplotype did not differ in patients vs. controls, the DR3/4-DQB1*0302 genotype had a RR of 12 (P<10-4). Moreover, a significant association of DQB1*0302 with the DR3/4 genotype was found (RR=3, P<10-2). In contrast, the distribution of DQB1*0401 alleles of DR4/X (X: other than 3, 4) is different from that of DR3/4 and DR4/4. Especially a significant association of DQB1*0401 with DR4/X (X: other than 1, 3, 4) was found (RR=3, P<10-3). The frequency of transmission of the DR4-DQB1*0302 haplotypes to diabetic offspring with DR3 was 80%, while to those without DR3 was 40%. In contrast, the transmission of the DR4-DQB1*0401 to those with DR3 was 60%, while to those without DR3 was 80%. High-risk DR4 subtypes were predominant in DR4/X (RR=7, P<10-3), whereas protective DR4 subtypes were observed mainly in the DR3/4 (RR=3, P<0.05). The association with diabetes and transmission to a diabetic offspring of DR4 haplotypes varies depending on the haplotype borne on the homologous chromosome. This might contribute not only to the synergistic effect of DR3/4, but also to the susceptibility influence of HLA DQB1*0401 alleles confined to DR4/X.

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