Low HERV-K(C4) copy number is associated with type 1 diabetes
- PMID: 24430436
- DOI: 10.2337/db13-1382
Low HERV-K(C4) copy number is associated with type 1 diabetes
Abstract
Complement component C4 (C4) is a highly variable complement pathway gene situated ∼500 kb from DRB1 and DQB1, the genes most strongly associated with many autoimmune diseases. Variations in C4 copy number (CN), length, and isotype create a highly diverse gene cluster in which insertion of an endogenous retrovirus in the ninth intron of C4, termed HERV-K(C4), is a notable component. We investigated the relationship between C4 variation/CN and type 1 diabetes. We found that individuals with type 1 diabetes have significantly fewer copies of HERV-K(C4) and that this effect is not solely due to linkage with known major histocompatibility complex class II susceptibility alleles. We show that HERV-K(C4) is a novel marker of type 1 diabetes that accounts for the disease association previously attributed to some key HLA-DQB1 alleles, raising the possibility that this retroviral insertion element contributes to functional protection against type 1 diabetes.
Similar articles
-
The variable endogenous retroviral insertion in the human complement C4 gene: a transmission study in type I diabetes mellitus.Hum Immunol. 2002 Jun;63(6):481-4. doi: 10.1016/s0198-8859(02)00398-1. Hum Immunol. 2002. PMID: 12039523
-
Detection of retroviral antisense transcripts and promoter activity of the HERV-K(C4) insertion in the MHC class III region.Immunogenetics. 2004 Aug;56(5):321-32. doi: 10.1007/s00251-004-0705-y. Epub 2004 Aug 12. Immunogenetics. 2004. PMID: 15309346
-
High-throughput analysis of the C4 polymorphism by a combination of MLPA and isotype-specific ELISA's.Mol Immunol. 2009 Feb;46(4):592-600. doi: 10.1016/j.molimm.2008.07.028. Epub 2008 Dec 5. Mol Immunol. 2009. PMID: 19062096
-
Dancing with complement C4 and the RP-C4-CYP21-TNX (RCCX) modules of the major histocompatibility complex.Prog Nucleic Acid Res Mol Biol. 2003;75:217-92. doi: 10.1016/s0079-6603(03)75007-7. Prog Nucleic Acid Res Mol Biol. 2003. PMID: 14604014 Review.
-
Polymorphism of the human complement component C4.Exp Clin Immunogenet. 1990;7(1):69-84. Exp Clin Immunogenet. 1990. PMID: 1971760 Review.
Cited by
-
Decrease in multiple complement proteins associated with development of islet autoimmunity and type 1 diabetes.iScience. 2023 Dec 20;27(2):108769. doi: 10.1016/j.isci.2023.108769. eCollection 2024 Feb 16. iScience. 2023. PMID: 38303689 Free PMC article.
-
Deletion of Vβ3+CD4+ T cells by endogenous mouse mammary tumor virus 3 prevents type 1 diabetes induction by autoreactive CD8+ T cells.Proc Natl Acad Sci U S A. 2023 Dec 5;120(49):e2312039120. doi: 10.1073/pnas.2312039120. Epub 2023 Nov 28. Proc Natl Acad Sci U S A. 2023. PMID: 38015847 Free PMC article.
-
Essential role of an ERV-derived Env38 protein in adaptive humoral immunity against an exogenous SVCV infection in a zebrafish model.PLoS Pathog. 2023 Apr 4;19(4):e1011222. doi: 10.1371/journal.ppat.1011222. eCollection 2023 Apr. PLoS Pathog. 2023. PMID: 37014912 Free PMC article.
-
Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis.NPJ Genom Med. 2022 Oct 5;7(1):57. doi: 10.1038/s41525-022-00327-8. NPJ Genom Med. 2022. PMID: 36198672 Free PMC article.
-
An Update Evolving View of Copy Number Variations in Autoimmune Diseases.Front Genet. 2022 Jan 20;12:794348. doi: 10.3389/fgene.2021.794348. eCollection 2021. Front Genet. 2022. PMID: 35126462 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous