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Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With DPB1*0201: Data From the Type 1 Diabetes Genetics Consortium.
Diabetes Care 2015; 38 Suppl 2:S21-8DC

Abstract

BACKGROUND

Autoimmune thyroiditis occurs in 10-25% of patients with type 1 diabetes (T1D). Most of these patients are also positive for thyroid peroxidase (TPO) antibodies. Thyroid dysfunction complicates T1D metabolic control and is a component of the autoimmune polyglandular syndrome (APS, type 2 or 3). Previous studies of isolated T1D and of T1D combined with other autoimmune disorders showed genetic susceptibility for alleles in HLA-DQB1 and -DRB1 and also CTLA4 and PTPN22.

RESEARCH DESIGN AND METHODS

We analyzed the Type 1 Diabetes Genetics Consortium Autoantibody Workshop data by differentiating those T1D probands with and without TPO antibodies or thyroid disease with respect to polymorphisms in HLA, CTLA4, INS, PTPN22, and VDR, taking into account the ethnic origin. Genotype and clinical/immunogenic phenotype data were analyzed by gene counting methods and logistic regression analysis.

RESULTS

The presence of TPO antibodies (25.2%) and thyroid disease (8.4%) was associated with older age, female sex, and presence of other autoantibodies (GAD65, ATPase, 21-OH) (all P<0.001). The highest prevalence was in patients of Hispanic ancestry (31%) and the lowest in those of African ancestry (8%). In T1D non-Hispanic whites, HLA-DRB1*0101 is significantly (P<0.0001) less frequent in TPO-positive than in TPO-negative individuals, whereas HLA-DRB1*0404, -DQB1*0301, and -DPB1*0201 are significantly (P<0.0001) more frequent. Subjects with a high titer of TPO autoantibodies and with thyroid disease were associated with female sex and older age and negatively associated with DRB1*0401-DQB1*0302 (P<0.0001). No significant differences were observed for an association of TPO positivity or thyroid disease with single nucleotide polymorphisms in the INS, CTLA4, or VDR loci, with nominal significance (P=0.01) for PTPN22 R620W variant.

CONCLUSIONS

Thyroid autoimmunity is highly prevalent in T1D patients of non-Hispanic white, Asian, or Hispanic origin. The strongest disease risk is conferred by female sex and older age. This risk is modulated by HLA-DRB1 and HLA-DPB1 loci. The immunogenetic profile for T1D with thyroid autoimmunity may identify distinct pathways regulating polyglandular autoimmunity and disease.

Authors+Show Affiliations

University Hospital Frankfurt, Frankfurt am Main, Germany.Barbara Davis Center for Childhood Diabetes, Aurora, CO.Barbara Davis Center for Childhood Diabetes, Aurora, CO.Barbara Davis Center for Childhood Diabetes, Aurora, CO.University Hospital Frankfurt, Frankfurt am Main, Germany badenhoop@em.uni-frankfurt.de.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26405068

Citation

Kahles, Heinrich, et al. "Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With DPB1*0201: Data From the Type 1 Diabetes Genetics Consortium." Diabetes Care, vol. 38 Suppl 2, 2015, pp. S21-8.
Kahles H, Fain PR, Baker P, et al. Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With DPB1*0201: Data From the Type 1 Diabetes Genetics Consortium. Diabetes Care. 2015;38 Suppl 2:S21-8.
Kahles, H., Fain, P. R., Baker, P., Eisenbarth, G., & Badenhoop, K. (2015). Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With DPB1*0201: Data From the Type 1 Diabetes Genetics Consortium. Diabetes Care, 38 Suppl 2, pp. S21-8. doi:10.2337/dcs15-2005.
Kahles H, et al. Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With DPB1*0201: Data From the Type 1 Diabetes Genetics Consortium. Diabetes Care. 2015;38 Suppl 2:S21-8. PubMed PMID: 26405068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With DPB1*0201: Data From the Type 1 Diabetes Genetics Consortium. AU - Kahles,Heinrich, AU - Fain,Pamela R, AU - Baker,Peter, AU - Eisenbarth,George, AU - Badenhoop,Klaus, PY - 2015/9/26/entrez PY - 2015/9/26/pubmed PY - 2016/5/4/medline SP - S21 EP - 8 JF - Diabetes care JO - Diabetes Care VL - 38 Suppl 2 N2 - BACKGROUND: Autoimmune thyroiditis occurs in 10-25% of patients with type 1 diabetes (T1D). Most of these patients are also positive for thyroid peroxidase (TPO) antibodies. Thyroid dysfunction complicates T1D metabolic control and is a component of the autoimmune polyglandular syndrome (APS, type 2 or 3). Previous studies of isolated T1D and of T1D combined with other autoimmune disorders showed genetic susceptibility for alleles in HLA-DQB1 and -DRB1 and also CTLA4 and PTPN22. RESEARCH DESIGN AND METHODS: We analyzed the Type 1 Diabetes Genetics Consortium Autoantibody Workshop data by differentiating those T1D probands with and without TPO antibodies or thyroid disease with respect to polymorphisms in HLA, CTLA4, INS, PTPN22, and VDR, taking into account the ethnic origin. Genotype and clinical/immunogenic phenotype data were analyzed by gene counting methods and logistic regression analysis. RESULTS: The presence of TPO antibodies (25.2%) and thyroid disease (8.4%) was associated with older age, female sex, and presence of other autoantibodies (GAD65, ATPase, 21-OH) (all P<0.001). The highest prevalence was in patients of Hispanic ancestry (31%) and the lowest in those of African ancestry (8%). In T1D non-Hispanic whites, HLA-DRB1*0101 is significantly (P<0.0001) less frequent in TPO-positive than in TPO-negative individuals, whereas HLA-DRB1*0404, -DQB1*0301, and -DPB1*0201 are significantly (P<0.0001) more frequent. Subjects with a high titer of TPO autoantibodies and with thyroid disease were associated with female sex and older age and negatively associated with DRB1*0401-DQB1*0302 (P<0.0001). No significant differences were observed for an association of TPO positivity or thyroid disease with single nucleotide polymorphisms in the INS, CTLA4, or VDR loci, with nominal significance (P=0.01) for PTPN22 R620W variant. CONCLUSIONS: Thyroid autoimmunity is highly prevalent in T1D patients of non-Hispanic white, Asian, or Hispanic origin. The strongest disease risk is conferred by female sex and older age. This risk is modulated by HLA-DRB1 and HLA-DPB1 loci. The immunogenetic profile for T1D with thyroid autoimmunity may identify distinct pathways regulating polyglandular autoimmunity and disease. SN - 1935-5548 UR - https://www.unboundmedicine.com/medline/citation/26405068/Genetics_of_Autoimmune_Thyroiditis_in_Type_1_Diabetes_Reveals_a_Novel_Association_With_DPB1_0201:_Data_From_the_Type_1_Diabetes_Genetics_Consortium_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=26405068 DB - PRIME DP - Unbound Medicine ER -