Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease.
OBJECTIVE
We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population.


METHODS
We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis.


RESULTS
The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects.


CONCLUSIONS
An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.
Takara
M
M
Second Department of Internal Medicine, University of the Ryukyus School of Medicine, Nishihara, Okinawa, Japan.
Komiya
I
I
Kinjo
Y
Y
Tomoyose
T
T
Yamashiro
S
S
Akamine
H
H
Masuda
M
M
Takasu
N
N
D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000409:Alanine; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood; D060908:CTLA-4 Antigen; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007515:Islets of Langerhans / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013912:Threonine; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001323:Autoantibodies; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007527:Isoenzymes; C024211:islet cell antibody; D013912:Threonine; D000069594:Abatacept; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D000409:Alanine