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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1789-1795
Number of pages7
JournalDiabetes
Volume63
Issue number5
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Endogenous Retroviruses
Type 1 Diabetes Mellitus
Alleles
Complement C4
Multigene Family
Major Histocompatibility Complex
Introns
Genes
Autoimmune Diseases

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., ... 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

Low HERV-K(C4) copy number is associated with type 1 diabetes. / Mason, Mike J.; Speake, Cate; Gersuk, Vivian H.; Nguyen, Quynh Anh; O'Brien, Kimberly K.; Odegard, Jared M.; Buckner, Jane H.; Greenbaum, Carla J.; Chaussabel, Damien J.; Nepom, Gerald T.

In: Diabetes, Vol. 63, No. 5, 2014, p. 1789-1795.

Research output: Contribution to journalArticle

Mason, MJ, Speake, C, Gersuk, VH, Nguyen, QA, O'Brien, KK, Odegard, JM, Buckner, JH, Greenbaum, CJ, Chaussabel, DJ & Nepom, GT 2014, 'Low HERV-K(C4) copy number is associated with type 1 diabetes', Diabetes, vol. 63, no. 5, pp. 1789-1795. https://doi.org/10.2337/db13-1382
Mason MJ, Speake C, Gersuk VH, Nguyen QA, O'Brien KK, Odegard JM et al. Low HERV-K(C4) copy number is associated with type 1 diabetes. Diabetes. 2014;63(5):1789-1795. https://doi.org/10.2337/db13-1382
Mason, Mike J. ; Speake, Cate ; Gersuk, Vivian H. ; Nguyen, Quynh Anh ; O'Brien, Kimberly K. ; Odegard, Jared M. ; Buckner, Jane H. ; Greenbaum, Carla J. ; Chaussabel, Damien J. ; Nepom, Gerald T. / Low HERV-K(C4) copy number is associated with type 1 diabetes. In: Diabetes. 2014 ; Vol. 63, No. 5. pp. 1789-1795.
@article{23d05eab43b645e086c5802da33d1d51,
title = "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.",
author = "Mason, {Mike J.} and Cate Speake and Gersuk, {Vivian H.} and Nguyen, {Quynh Anh} and O'Brien, {Kimberly K.} and Odegard, {Jared M.} and Buckner, {Jane H.} and Greenbaum, {Carla J.} and Chaussabel, {Damien J.} and Nepom, {Gerald T.}",
year = "2014",
doi = "10.2337/db13-1382",
language = "English",
volume = "63",
pages = "1789--1795",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "5",

}

TY - JOUR

T1 - Low HERV-K(C4) copy number is associated with type 1 diabetes

AU - Mason, Mike J.

AU - Speake, Cate

AU - Gersuk, Vivian H.

AU - Nguyen, Quynh Anh

AU - O'Brien, Kimberly K.

AU - Odegard, Jared M.

AU - Buckner, Jane H.

AU - Greenbaum, Carla J.

AU - Chaussabel, Damien J.

AU - Nepom, Gerald T.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84899126426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899126426&partnerID=8YFLogxK

U2 - 10.2337/db13-1382

DO - 10.2337/db13-1382

M3 - Article

VL - 63

SP - 1789

EP - 1795

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 5

ER -