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 Chaussabel and
- Gerald T. Nepom
- Corresponding author: Mike J. Mason, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-1382/-/DC1.
- Received September 6, 2013.
- Accepted January 7, 2014.
- © 2014 by the American Diabetes Association.
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