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Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity
- Source :
- Gutierrez-Achury, J, Romanos, J, Bakker, S F, Kumar, V, de Haas, E C, Trynka, G, Ricano-Ponce, I, Steck, A, Chen, W M, Onengut-Gumuscu, S, Simsek, S, Rewers, M, Mulder, C J, Liu, E, Rich, S S & Wijmenga, C 2015, ' Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity ', Diabetes Care, vol. 38, pp. S37-S44 . https://doi.org/10.2337/dcs15-2007, Diabetes Care, Diabetes Care, 38, S37-S44, Diabetes Care, 38, S37-S44. AMER DIABETES ASSOC, Diabetes Care, 38, S37-S44. American Diabetes Association Inc.
- Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Male
Endocrinology, Diabetes and Metabolism
LOCI
Autoimmunity
Genome-wide association study
CHILDREN
Disease
medicine.disease_cause
Linkage Disequilibrium
0302 clinical medicine
Gene Frequency
HLA Antigens
Genotype
Odds Ratio
RISK VARIANTS
IMMUNE-RESPONSE
CTLA-4 Antigen
MULTIPLE COMMON
GENERAL-POPULATION
0303 health sciences
3. Good health
Female
Genetic Background
Risk
endocrine system
030209 endocrinology & metabolism
Single-nucleotide polymorphism
Human leukocyte antigen
Polymorphism, Single Nucleotide
SHARED GENETICS
03 medical and health sciences
Internal Medicine
medicine
Humans
Genetic Predisposition to Disease
GENOME-WIDE ASSOCIATION
Genetic Association Studies
METAANALYSIS
030304 developmental biology
Advanced and Specialized Nursing
business.industry
Haplotype
fungi
CONSORTIUM
Interleukin-2 Receptor alpha Subunit
nutritional and metabolic diseases
Type 1 Diabetes Genetics Consortium (T1DGC) Autoantibody Workshop
Odds ratio
Celiac Disease
Diabetes Mellitus, Type 1
Haplotypes
Genetic Loci
Case-Control Studies
Immunology
business
Subjects
Details
- Language :
- English
- ISSN :
- 01495992
- Database :
- OpenAIRE
- Journal :
- Gutierrez-Achury, J, Romanos, J, Bakker, S F, Kumar, V, de Haas, E C, Trynka, G, Ricano-Ponce, I, Steck, A, Chen, W M, Onengut-Gumuscu, S, Simsek, S, Rewers, M, Mulder, C J, Liu, E, Rich, S S & Wijmenga, C 2015, ' Contrasting the Genetic Background of Type 1 Diabetes and Celiac Disease Autoimmunity ', Diabetes Care, vol. 38, pp. S37-S44 . https://doi.org/10.2337/dcs15-2007, Diabetes Care, Diabetes Care, 38, S37-S44, Diabetes Care, 38, S37-S44. AMER DIABETES ASSOC, Diabetes Care, 38, S37-S44. American Diabetes Association Inc.
- Accession number :
- edsair.doi.dedup.....985f868978241bb4d540105cdd7ab58d
- Full Text :
- https://doi.org/10.2337/dcs15-2007