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PMID: 3139557 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The susceptibility to insulin-dependent diabetes mellitus is associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3,4 heterozygotes.

Immunogenetics ·Vol. 28 ·No. 5 ·1988-00-00 ·Pages 320-7

Thomsen M, Mølvig J, Zerbib A, de Preval C, Abbal M, Dugoujon JM, Ohayon E, Svejgaard A, Cambon-Thomsen A, Nerup J

Abstract

In the genetically homogeneous Danish population, 27 HLA-DR3,4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM) and 19 DR3,4 heterozygous controls without family history of IDDM were investigated for HLA-region markers and Gm and Km immunoglobulin allotypes. The aim was to define susceptibility factors for IDDM development other than HLA-DR using a number of techniques: lymphocytotoxicity (HLA-DR and DQ antigens), cellular methods (Dw and DP typing), restriction fragment length polymorphism (DQ alleles), electrophoresis and immunofixation (BF and C4 allotypes), and passive hemagglutination inhibition (Gm and Km immunoglobulin allotypes). The complement allotype C4A3 and the HLA-DQw8 (DQw3.2) antigen were found in all of the patients, whereas this was the case for only 8 of the 19 controls (P = 6 x 10(-6)): five lacked C4A3, five others lacked DQw8, and one of the controls lacked both of these factors. Fourteen of the patients had the complement allotype C4B3 versus three of the controls (P = 0.01). Previously reported family studies suggest that these alleles are part of the following haplotype: B15, BFS, C4A3, C4B3, DR4, Dw4, DQw8, and these factors were found together in ten of the patients versus one of the controls (P = 0.01). The markers usually associated with DR3 did not show significant differences between IDDM patients and controls, and the non-HLA markers studied showed no significant deviation from what was expected. In addition to the susceptibility factor DQw8, the study suggests the existence of susceptibility genes for IDDM near the complement C4 genes on DR4-carrying haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms
Complement C4/genetics Diabetes Mellitus, Type 1/genetics Gene Frequency Genes, Immunoglobulin Genes, MHC Class II HLA-DQ Antigens/genetics Haplotypes Heterozygote Humans Immunoglobulin Allotypes/genetics
Chemicals
Complement C4 HLA-DQ Antigens Immunoglobulin Allotypes
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Thomsen M
INSERM U. 100, CHU Purpan, Toulouse, France.
Mølvig J
Zerbib A
de Preval C
Abbal M
Dugoujon J M
Ohayon E
Svejgaard A
Cambon-Thomsen A
Nerup J
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Article Info
Journal
Immunogenetics
Abbr.
Immunogenetics
ISSN
0093-7711
DOI
10.1007/BF00364230
Published
1988-00-00
Pages
320-7
Language
English
Region
United States
NLM ID
0420404
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00364230 View journal details
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