RGD Reference Report - Clinical and genetic characteristics of patients with autoimmune thyroid disease with anti-islet autoimmunity. - Rat Genome Database

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Clinical and genetic characteristics of patients with autoimmune thyroid disease with anti-islet autoimmunity.

Authors: Moriguchi, M  Noso, S  Kawabata, Y  Yamauchi, T  Harada, T  Komaki, K  Babaya, N  Hiromine, Y  Ito, H  Yamagata, S  Murata, K  Higashimoto, T  Park, C  Yamamoto, A  Ohno, Y  Ikegami, H 
Citation: Moriguchi M, etal., Metabolism. 2011 Jun;60(6):761-6. Epub 2010 Sep 9.
RGD ID: 5147571
Pubmed: PMID:20825955   (View Abstract at PubMed)
DOI: DOI:10.1016/j.metabol.2010.07.025   (Journal Full-text)

In contrast to the large number of studies on autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus, little is known about the anti-islet autoimmune status in patients with autoimmune thyroid diseases (AITDs). We therefore studied the anti-islet autoimmune status in patients with AITD and the clinical and genetic characteristics of AITD patients with anti-islet autoimmunity. The positivity and titer of glutamic acid decarboxylase antibody (GAD Ab) were studied in 866 Japanese patients with AITD (546 with Graves disease and 320 with Hashimoto thyroiditis), 221 patients with thyroid disease of nonautoimmune origin, and 282 control subjects. The clinical characteristics and genotypes of HLA-DRB1, DQB1, and CTLA4 were compared between AITD patients with and without GAD Ab. The prevalence of GAD Ab was significantly higher in AITD patients than in control subjects (5.8% vs 2.1%, P = .01), particularly in Graves disease (7.1% vs 2.1%, P = .0019). The prevalence of diabetes mellitus was significantly higher in AITD patients with GAD Ab than in those without (40.0% vs 10.1%, P < .0001), particularly in those with a high titer of GAD Ab (high vs low titer: 64% vs 16%, P = .001) and also in those positive for insulinoma-associated antigen 2 (IA-2) Ab (IA-2 positive vs negative: 75.0% vs 31.3%, P = .016). The AITD patients with GAD Ab were characterized by younger age at onset of diabetes, lower body mass index, higher hemoglobin A(1c) level, and higher frequency of insulin therapy than those without GAD Ab. The frequency of the DRB1*0405-DQB1*0401 haplotype was significantly higher in AITD patients with GAD Ab than in those without GAD Ab and control subjects. A single nucleotide polymorphism (rs3087243) of CTLA4 was significantly associated with AITD, but not with positivity of GAD Ab. These results indicate that patients with AITD, and in particular Graves disease, are prone to develop beta-cell autoimmunity and insulin-requiring diabetes, particularly those with a high titer of GAD Ab and/or positive for both GAD and IA-2 Ab. Glutamic acid decarboxylase Ab positivity in AITD patients was associated with HLA, conferring susceptibility to type 1 diabetes mellitus.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
H2-Ab1Mouseautoimmune thyroiditis  ISOHLA-DQB1 (Homo sapiens)DNA:polymorphisms and haplotype:cds:HLA-DQB1*0401 (human)RGD 
H2-Eb1Mouseautoimmune thyroiditis  ISOHLA-DRB1 (Homo sapiens)DNA:polymorphism (human)RGD 
HLA-DQB1Humanautoimmune thyroiditis  IAGP DNA:polymorphisms and haplotype:cds:HLA-DQB1*0401 (human)RGD 
HLA-DRB1Humanautoimmune thyroiditis  IAGP DNA:polymorphism (human)RGD 
RT1-BbRatautoimmune thyroiditis  ISOHLA-DQB1 (Homo sapiens)DNA:polymorphisms and haplotype:cds:HLA-DQB1*0401 (human)RGD 
RT1-Db1Ratautoimmune thyroiditis  ISOHLA-DRB1 (Homo sapiens)DNA:polymorphism (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
RT1-Bb  (RT1 class II, locus Bb)
RT1-Db1  (RT1 class II, locus Db1)

Genes (Mus musculus)
H2-Ab1  (histocompatibility 2, class II antigen A, beta 1)
H2-Eb1  (histocompatibility 2, class II antigen E beta)

Genes (Homo sapiens)
HLA-DQB1  (major histocompatibility complex, class II, DQ beta 1)
HLA-DRB1  (major histocompatibility complex, class II, DR beta 1)


Additional Information