Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity

Type 1 diabetes (T1D) and celiac disease (CeD) cluster in families and can occur in the same individual. Genetic loci have been associated with susceptibility to both diseases. Our aim was to explore the genetic differences between individuals developing both these diseases (double autoimmunity) ver...

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Main Authors: Gutierrez-Achury, Javier, Romanos, Jihane, Bakker, Sjoerd F., Kumar, Vinod, de Haas, Esther C., Trynka, Gosia, Ricaño-Ponce, Isis, Steck, Andrea, Chen, Wei-Min, Onengut-Gumuscu, Suna, Simsek, Suat, Rewers, Marian, Mulder, Chris J., Liu, Ed, Rich, Stephen S., Wijmenga, Cisca
Format: Online
Language:English
Published: American Diabetes Association 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582914/
id pubmed-4582914
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spelling pubmed-45829142016-10-01 Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity Gutierrez-Achury, Javier Romanos, Jihane Bakker, Sjoerd F. Kumar, Vinod de Haas, Esther C. Trynka, Gosia Ricaño-Ponce, Isis Steck, Andrea Chen, Wei-Min Onengut-Gumuscu, Suna Simsek, Suat Rewers, Marian Mulder, Chris J. Liu, Ed Rich, Stephen S. Wijmenga, Cisca Type 1 Diabetes Genetics Consortium (T1DGC) Autoantibody Workshop Type 1 diabetes (T1D) and celiac disease (CeD) cluster in families and can occur in the same individual. Genetic loci have been associated with susceptibility to both diseases. Our aim was to explore the genetic differences between individuals developing both these diseases (double autoimmunity) versus those with only one. We hypothesized that double autoimmunity individuals carry more of the genetic risk markers that are shared between the two diseases independently. SNPs were genotyped in loci associated with T1D (n = 42) and CeD (n = 28) in 543 subjects who developed double autoimmunity, 2,472 subjects with T1D only, and 2,223 CeD-only subjects. For identification of loci that were specifically associated with individuals developing double autoimmunity, two association analyses were conducted: double autoimmunity versus T1D and double autoimmunity versus CeD. HLA risk haplotypes were compared between the two groups. The CTLA4 and IL2RA loci were more strongly associated with double autoimmunity than with either T1D or CeD alone. HLA analyses indicated that the T1D high-risk genotype, DQ2.5/DQ8, provided the highest risk for developing double autoimmunity (odds ratio 5.22, P = 2.25 × 10−29). We identified a strong HLA risk genotype (DQ2.5/DQ8) predisposing to double autoimmunity, suggesting a dominant role for HLA. Non-HLA loci, CTLA4 and IL2RA, may also confer risk to double autoimmunity. Thus, CeD patients who carry the DQ2.5/DQ8 genotype may benefit from periodic screening of autoantibodies related to T1D. American Diabetes Association 2015-10 2015-09-18 /pmc/articles/PMC4582914/ /pubmed/26405070 http://dx.doi.org/10.2337/dcs15-2007 Text en © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Gutierrez-Achury, Javier
Romanos, Jihane
Bakker, Sjoerd F.
Kumar, Vinod
de Haas, Esther C.
Trynka, Gosia
Ricaño-Ponce, Isis
Steck, Andrea
Chen, Wei-Min
Onengut-Gumuscu, Suna
Simsek, Suat
Rewers, Marian
Mulder, Chris J.
Liu, Ed
Rich, Stephen S.
Wijmenga, Cisca
spellingShingle Gutierrez-Achury, Javier
Romanos, Jihane
Bakker, Sjoerd F.
Kumar, Vinod
de Haas, Esther C.
Trynka, Gosia
Ricaño-Ponce, Isis
Steck, Andrea
Chen, Wei-Min
Onengut-Gumuscu, Suna
Simsek, Suat
Rewers, Marian
Mulder, Chris J.
Liu, Ed
Rich, Stephen S.
Wijmenga, Cisca
Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity
author_facet Gutierrez-Achury, Javier
Romanos, Jihane
Bakker, Sjoerd F.
Kumar, Vinod
de Haas, Esther C.
Trynka, Gosia
Ricaño-Ponce, Isis
Steck, Andrea
Chen, Wei-Min
Onengut-Gumuscu, Suna
Simsek, Suat
Rewers, Marian
Mulder, Chris J.
Liu, Ed
Rich, Stephen S.
Wijmenga, Cisca
author_sort Gutierrez-Achury, Javier
title Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity
title_short Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity
title_full Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity
title_fullStr Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity
title_full_unstemmed Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity
title_sort contrasting the genetic background of type 1 diabetes and celiac disease autoimmunity
description Type 1 diabetes (T1D) and celiac disease (CeD) cluster in families and can occur in the same individual. Genetic loci have been associated with susceptibility to both diseases. Our aim was to explore the genetic differences between individuals developing both these diseases (double autoimmunity) versus those with only one. We hypothesized that double autoimmunity individuals carry more of the genetic risk markers that are shared between the two diseases independently. SNPs were genotyped in loci associated with T1D (n = 42) and CeD (n = 28) in 543 subjects who developed double autoimmunity, 2,472 subjects with T1D only, and 2,223 CeD-only subjects. For identification of loci that were specifically associated with individuals developing double autoimmunity, two association analyses were conducted: double autoimmunity versus T1D and double autoimmunity versus CeD. HLA risk haplotypes were compared between the two groups. The CTLA4 and IL2RA loci were more strongly associated with double autoimmunity than with either T1D or CeD alone. HLA analyses indicated that the T1D high-risk genotype, DQ2.5/DQ8, provided the highest risk for developing double autoimmunity (odds ratio 5.22, P = 2.25 × 10−29). We identified a strong HLA risk genotype (DQ2.5/DQ8) predisposing to double autoimmunity, suggesting a dominant role for HLA. Non-HLA loci, CTLA4 and IL2RA, may also confer risk to double autoimmunity. Thus, CeD patients who carry the DQ2.5/DQ8 genotype may benefit from periodic screening of autoantibodies related to T1D.
publisher American Diabetes Association
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582914/
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