HLA haplotypes in Type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus View Full Text


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Article Info

DATE

1992-03

AUTHORS

P. J. Tienari, E. Tuomilehto-Wolf, J. Tuomilehto, L. Peltonen, H. K. Åkerblom, A. Fagerlund, M. Flittner, B. Gustafsson, A. Hakulinen, L. Herva, P. Hiltunen, T. Huhtamäki, N. P. Huttunen, T. Huupponen, M. Hyttinen, Ch. Häggqvist, T. Joki, R. Jokisalo, S. Kallio, E. A. Kaprio, U. Kaski, M. Knip, M. L. Käär, L. Laine, J. Lappalainen, J. Mäenpää, A. L. Mäkelä, K. Niemi, A. Niiranen, P. Ojajärvi, T. Otonkoski, K. Pihlajamäki, S. Pöntynen, J. Sankala, J. Schumacher, M. Sillanpää, C. H. Stråhlmann, M. R. Ståhlberg, T. Uotila, P. Varimo, M. Väre

ABSTRACT

In Caucasians the predisposition to Type 1 (insulin-dependent) diabetes mellitus has been shown to associate with HLA-DR3,DQw2 and DR4,DQw8 and with the presence of amino acids other than aspartic acid at position 57 on the HLA-DQβ chain. In Finland the haplotype-specific absolute risk for developing Type 1 diabetes differs between various DR3 and DR4 positive haplotypes. The aim of our present analysis was to find out whether this variation is attributable to polymorphism at the DQ locus. As part of a nationwide prospective study including 757 serologically HLA genotyped families, we determined HLA-DQα and DQβ restriction fragment polymorphisms in 17 selected families with important susceptibility haplotypes. Additionally, the DQA1 alleles were determined from 19 haplotypes using sequence-specific oligonucleotide probes, and the DQB1 second exon was sequenced from nine haplotypes. The DR3 as well as DR4 positive haplotypes frequently found in Type 1 diabetic patients showed no variation at the HLA-DQ locus, and they were DQw2 and DQw8, respectively. The absolute risk for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4 A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was 35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively. The absolute risks for DR3,DQw2 positive haplotypes A1, Cw7,B8,DR3 and A2,Cw7,B8,DR3 were 68/100,000 and 103/100,000, respectively. These results provide further evidence that not only the polymorphism at the DQ locus but also other genes of the haplotypes contribute to susceptibility to Type 1 diabetes. More... »

PAGES

254-260

References to SciGraph publications

  • 1989. RFLP Standardization Report for DQ Alpha/PstI in IMMUNOBIOLOGY OF HLA
  • 1987-10. HLA-DQβ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus in NATURE
  • 1989. RFLP Standardization Report for DQ Alpha/TaqI in IMMUNOBIOLOGY OF HLA
  • 1989. RFLP Standardization Report for DQ Beta/BamHI in IMMUNOBIOLOGY OF HLA
  • 1989. RFLP Standardization Report for DR Beta/TaqI in IMMUNOBIOLOGY OF HLA
  • 1989. Towards a Physical Map of the HLA Complex in IMMUNOBIOLOGY OF HLA
  • 1990-04. Heterogeneity of HLA genetic factors in IDDM susceptibility in IMMUNOGENETICS
  • 1987-01. Structure and expression of HLA-DQα and -DXα genes: interallelic alternate splicing of the HLA-DQα gene and functional splicing of the HLA-DXα gene using a retroviral vector in IMMUNOGENETICS
  • 1988-11. The susceptibility to insulin-dependent diabetes mellitus bis associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3, 4 heterozygotes in IMMUNOGENETICS
  • 1989-10. Aspartic acid at position 57 of DQβ chain does not protect against Type 1 (insulin-dependent) diabetes mellitus in Japanese subjects in DIABETOLOGIA
  • 1989. RFLP Standardization Report for DQ Beta/PstI in IMMUNOBIOLOGY OF HLA
  • 1983-06. HLA-D region β-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals in NATURE
  • 1987-07. Allelic forms of the alpha- and beta-chain genes encoding DQw1-positive heterodimers in IMMUNOGENETICS
  • 1986. Molecular Genetics of the Human Major Histocompatibility Complex in ADVANCES IN HUMAN GENETICS 15
  • 1972. The Finnish population structure A genetic and genealogical study in HEREDITAS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/bf00400926

    DOI

    http://dx.doi.org/10.1007/bf00400926

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1026776956

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/1348711


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