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 - PubMed (original) (raw)

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

M Thomsen et al. Immunogenetics. 1988.

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)

PubMed Disclaimer

Cited by

Contribution of Retrotransposons to the Pathogenesis of Type 1 Diabetes and Challenges in Analysis Methods.
Štangar A, Kovač J, Šket R, Tesovnik T, Zajec A, Čugalj Kern B, Jenko Bizjan B, Battelino T, Dovč K. Štangar A, et al. Int J Mol Sci. 2023 Feb 4;24(4):3104. doi: 10.3390/ijms24043104. Int J Mol Sci. 2023. PMID: 36834511 Free PMC article. Review.
The predisposition to type 1 diabetes linked to the human leukocyte antigen complex includes at least one non-class II gene.
Lie BA, Todd JA, Pociot F, Nerup J, Akselsen HE, Joner G, Dahl-Jørgensen K, Rønningen KS, Thorsby E, Undlien DE. Lie BA, et al. Am J Hum Genet. 1999 Mar;64(3):793-800. doi: 10.1086/302283. Am J Hum Genet. 1999. PMID: 10053014 Free PMC article.
Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis.
Mulcahy B, Waldron-Lynch F, McDermott MF, Adams C, Amos CI, Zhu DK, Ward RH, Clegg DO, Shanahan F, Molloy MG, O'Gara F. Mulcahy B, et al. Am J Hum Genet. 1996 Sep;59(3):676-83. Am J Hum Genet. 1996. PMID: 8751869 Free PMC article.
A new marker in the HLA class I region is associated with the age at onset of IDDM.
Demaine AG, Hibberd ML, Mangles D, Millward BA. Demaine AG, et al. Diabetologia. 1995 May;38(5):623-8. doi: 10.1007/BF00400734. Diabetologia. 1995. PMID: 7489848
TNF-alpha gene polymorphisms in type 1 (insulin-dependent) diabetes mellitus.
Badenhoop K, Schwarz G, Trowsdale J, Lewis V, Usadel KH, Gale EA, Bottazzo GF. Badenhoop K, et al. Diabetologia. 1989 Jul;32(7):445-8. doi: 10.1007/BF00271265. Diabetologia. 1989. PMID: 2572498

References

1. Tissue Antigens. 1980 Feb;15(2):123-36 - PubMed
1. Diabetologia. 1986 Jan;29(1):63-7 - PubMed
1. Tissue Antigens. 1986 May;27(5):256-61 - PubMed
1. Tissue Antigens. 1982 Aug;20(2):123-40 - PubMed
1. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8699-702 - PubMed

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 - PubMed (original) (raw)