Low HERV-K(C4) copy number is associated with type 1 diabetes

Mike J. Mason, Cate Speake, Vivian H. Gersuk, Quynh Anh Nguyen, Kimberly K. O'Brien, Jared M. Odegard, Jane H. Buckner, Carla J. Greenbaum, Damien J. Chaussabel, Gerald T. Nepom

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19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1789-1795
Number of pages7
Issue number5
Publication statusPublished - 2014
Externally publishedYes


ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Mason, M. J., Speake, C., Gersuk, V. H., Nguyen, Q. A., O'Brien, K. K., Odegard, J. M., Buckner, J. H., Greenbaum, C. J., Chaussabel, D. J., & Nepom, G. T. (2014). Low HERV-K(C4) copy number is associated with type 1 diabetes. Diabetes, 63(5), 1789-1795. https://doi.org/10.2337/db13-1382