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PMID: 1974216 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

HLA-DQ beta-chain restriction fragment length polymorphism as a risk marker in type 1 (insulin-dependent) diabetes mellitus: a Finnish family study.

Diabetologia ·Vol. 33 ·No. 6 ·1990-06-00 ·Pages 357-62

Reijonen H, Ilonen J, Knip M, Michelsen B, Akerblom HK

Abstract

Finnish Type 1 (insulin-dependent) diabetic families were analysed for HLA-DQ beta-chain polymorphism using a short intron-specific probe. A simple hybridization pattern was obtained in which all fragments were associated significantly with Type 1 diabetes. The simultaneous presence of two different risk markers, the allelic 12-kilobase and 4-kilobase fragments were strongly associated with Type 1 diabetes since 50% of the patients had this combination compared with only 2% of the control subjects. The cosegregated 7.5/3.0 kilobase fragments, which were associated with HLA-DR2 and DRw6 were not detected among the diabetic patients but were present in 48% of the control subjects. Our results provide further support for the location of susceptibility determining factors in the HLA-DQ gene area. The clear-cut, simple restriction fragment length polymorphism pattern obtained here, which bears a resemblance to a two allelic system, therefore makes this method applicable for estimating the risk of Type 1 diabetes at the population level.

MeSH Terms
Adolescent Alleles B-Lymphocytes/immunology Biomarkers/analysis Child Deoxyribonuclease BamHI Diabetes Mellitus, Type 1/genetics,immunology Finland Genotype HLA-DQ Antigens/genetics HLA-DQ beta-Chains HLA-DR Antigens/genetics Haplotypes Humans Polymorphism, Restriction Fragment Length Reference Values Risk Factors
Chemicals
Biomarkers HLA-DQ Antigens HLA-DQ beta-Chains HLA-DQbeta antigen HLA-DR Antigens Deoxyribonuclease BamHI
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Reijonen H
Department of Medical Microbiology, University of Oulu, Denmark.
Ilonen J
Knip M
Michelsen B
Akerblom H K
References (28)
28 references, click to expand
  1. A systematic study of HLA class II-beta DNA restriction fragments in insulin-dependent diabetes mellitus.
    Proc Natl Acad Sci U S A. 1985 May;82(10):3335-9 PMID: 2987920
  2. Sequence analysis of HLA class II genes from insulin-dependent diabetic individuals.
    Hum Immunol. 1988 Apr;21(4):249-63 PMID: 3372263
  3. DQ Wa gives rise to a DQ beta restriction fragment pattern indistinguishable from that of the DQw3.2 sub-type of DQw3.
    Tissue Antigens. 1988 Jul;32(1):41-5 PMID: 2903583
  4. Aspartic acid at position 57 of the HLA-DQ beta chain protects against type I diabetes: a family study.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):8111-5 PMID: 3186714
  5. Islet cell and insulin autoantibodies in subjects at high risk for development of type 1 (insulin-dependent) diabetes mellitus: the Lyon family study.
    Diabetologia. 1988 Oct;31(10):741-6 PMID: 3071483
  6. HLA associations in insulin-dependent diabetes: search for heterogeneity in different groups of patients from a homogeneous population.
    Tissue Antigens. 1986 Oct;28(4):237-44 PMID: 3492782
  7. A diabetes-susceptible HLA haplotype is best defined by a combination of HLA-DR and -DQ alleles.
    J Clin Invest. 1989 Mar;83(3):830-5 PMID: 2784133
  8. HLA-DO polymorphism associated with resistance to type I diabetes detected with monoclonal antibodies, isoelectric point differences, and restriction fragment length polymorphism.
    J Exp Med. 1986 Sep 1;164(3):938-43 PMID: 3462303
  9. HLA-D region beta-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals.
    Nature. 1983 Jun 30;303(5920):815-7 PMID: 6306468
  10. The epidemiology of insulin-dependent diabetes mellitus (IDDM) in Finland and in northern Europe.
    Diabetes Care. 1985 Sep-Oct;8 Suppl 1:10-6 PMID: 3863753
  11. Analysis of DR and DQ gene products of the DR4 haplotype in patients with IDDM: possible involvement of more than one locus.
    Hum Immunol. 1988 Dec;23(4):289-99 PMID: 3266208
  12. An increased risk of insulin-dependent diabetes mellitus (IDDM) among HLA-DR4,DQw8/DRw8,DQw4 heterozygotes.
    Hum Immunol. 1989 Mar;24(3):165-73 PMID: 2564383
  13. Definition of IDDM-associated HLA DQ and DX RFLPs by segregation analysis of multiplex sibships.
    Hum Immunol. 1989 Jan;24(1):51-63 PMID: 2563360
  14. Detection of specific sequences among DNA fragments separated by gel electrophoresis.
    J Mol Biol. 1975 Nov 5;98(3):503-17 PMID: 1195397
  15. Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin-dependent diabetes mellitus with HLA-DQ.
    J Clin Invest. 1987 Apr;79(4):1144-52 PMID: 2881947
  16. Only one DQ-beta restriction fragment pattern of each DR specificity is associated with insulin-dependent diabetes.
    J Immunol. 1986 Aug 1;137(3):941-7 PMID: 2424992
  17. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus.
    Nature. 1987 Oct 15-21;329(6140):599-604 PMID: 3309680
  18. Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese HLA antigens and organ-specific autoantibodies.
    Diabetologia. 1989 Jan;32(1):34-9 PMID: 2651187
  19. HLA DQ alpha and DQ beta restriction fragment length polymorphisms associated with Felty's syndrome and DR4-positive rheumatoid arthritis.
    Hum Immunol. 1987 Aug;19(4):269-78 PMID: 2445715
  20. Specific genomic markers for the HLA-DQ subregion discriminate between DR4+ insulin-dependent diabetes mellitus and DR4+ seropositive juvenile rheumatoid arthritis.
    J Exp Med. 1986 Jul 1;164(1):345-50 PMID: 3014039
  21. HLA class II genes polymorphism in DR4 giant cell arteritis patients.
    Tissue Antigens. 1988 Nov;32(5):254-8 PMID: 2906182
  22. Study of cis and trans interactions between extended HLA-haplotypes in insulin-dependent diabetes.
    Tissue Antigens. 1988 May;31(5):259-69 PMID: 3400091
  23. Molecular diversity of HLA-DR4 haplotypes.
    Proc Natl Acad Sci U S A. 1986 Apr;83(8):2642-6 PMID: 3458223
  24. Polymorphisms of DQ beta genes in HLA-DR4 haplotypes from healthy and diabetic individuals.
    Immunogenetics. 1987;25(3):152-60 PMID: 2881884
  25. Extended HLA haplotypes in families with insulin-dependent diabetes mellitus in northern Finland.
    Tissue Antigens. 1988 Sep;32(3):139-44 PMID: 3217930
  26. HLA typing data on 100 type 1 (insulin-dependent) diabetic patients from central Italy show a negative association with DR5 rather than with DR2.
    Clin Immunol Immunopathol. 1987 Oct;45(1):143-6 PMID: 3497749
  27. A DR4-associated DR-DQ haplotype is significantly associated with rheumatoid arthritis.
    Arthritis Rheum. 1988 Jan;31(1):72-9 PMID: 2830890
  28. HLA-DQ system and insulin-dependent diabetes mellitus in Japanese: does it contribute to the development of IDDM as it does in Caucasians?
    Immunogenetics. 1988;28(4):240-6 PMID: 2901399
Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
Published
1990-06-00
Pages
357-62
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
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