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CTLA4 gene polymorphism contributes to the mode of onset of diabetes with antiglutamic acid decarboxylase antibody in Japanese patients: genetic analysis of diabetic patients with antiglutamic acid decarboxylase antibody
Author(s) -
Abe T.,
Yamaguchi Y.,
Takino H.,
Fujita N.,
YamauchiDegawa M.,
Ozaki M.,
Yamakawa K.,
Sera Y.,
Sakamaki H.,
Uotani S.,
Kawasaki E.,
Awata T.,
Yamasaki H.,
Eguchi K.
Publication year - 2001
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1046/j.0742-3071.2001.00551.x
Subject(s) - glutamate decarboxylase , diabetes mellitus , allele , medicine , endocrinology , variable number tandem repeat , human leukocyte antigen , polymorphism (computer science) , gene , genetics , immunology , biology , antigen , enzyme , biochemistry
Aim The mode of onset is occasionally similar in Type 1 and Type 2 diabetes mellitus, and some patients with Type 2 diabetes are positive for antiglutamic acid decarboxylase antibody (GAD Ab). We investigated the contribution of Type 1 diabetes susceptibility genes to the progression of the insulin‐deficient state and mode of onset of Type 2 diabetes in GAD Ab‐positive (GAD‐Ab + ) patients. We examined the variable number of tandem repeats in the promoter region of the insulin gene (INS‐VNTR, insulin‐dependent diabetes mellitus (IDDM) 2) and cytotoxic T lymphocyte antigen 4 (CTLA4, IDDM12) as representative of Type 1 diabetes susceptibility genes. Methods Patients with Type 2 diabetes who were GAD‐Ab + ( n = 51) were selected for this study. In INS‐VNTR, the class I allele was classified according to length (1S, 25–38 repeat units; 1M, 39–41 repeat units; 1L, 42–44 repeat units) and the exact class I allele length was analysed by specific polymerase chain reaction (PCR) amplifications. Analyses of classes II and III were performed by Southern blot. CTLA4 gene polymorphism (exon 1 position 49, G/A) was analysed by PCR–restriction fragment length polymorphism. Results The distribution of INS‐VNTR was no different between Type 1 diabetes and Type 2 diabetes with GAD Ab. The allele frequencies of CTLA4 gene polymorphism G and A in Type 2 diabetes/GAD‐Ab + were significantly different from those of Type 1 diabetes/GAD‐Ab + (G: 53%, A: 47% vs. G: 84%, A: 16%; P < 0.0001). Conclusions Our data showed that GAD‐Ab + Japanese patients presenting with Type 2 diabetes have shifted A allele while patients with abrupt onset have shifted G allele of CTLA4 gene polymorphism. Our results suggest that immunological function and polymorphism of the CTLA4 gene may contribute to the pathogenesis and progression of Type 1 diabetes. Diabet. Med. 18, 726–731 (2001)