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

Tissue Antigens. 2001 Mar;57(3):185-91. doi: 10.1034/j.1399-0039.2001.057003185.x.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Child
  • Diabetes Mellitus, Type 1 / genetics*
  • European Continental Ancestry Group / genetics
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease
  • HLA-DQ Antigens / genetics*
  • HLA-DR Antigens / genetics*
  • HLA-DR4 Antigen / genetics
  • Haplotypes*
  • Humans
  • Sequence Homology, Nucleic Acid

Substances

  • HLA-DQ Antigens
  • HLA-DR Antigens
  • HLA-DR4 Antigen