Diabetes Care, Vol 23, Issue 7 975-978, Copyright © 2000 by American Diabetes Association

ARTICLES

Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease

M Takara, I Komiya, Y Kinjo, T Tomoyose, S Yamashiro, H Akamine, M Masuda and N Takasu
Second Department of Internal Medicine, University of the Ryukyus School of Medicine, Nishihara, Okinawa, Japan.

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. RESEARCH DESIGN AND 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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Huber, F. Menconi, S. Corathers, E. M. Jacobson, and Y. Tomer Joint Genetic Susceptibility to Type 1 Diabetes and Autoimmune Thyroiditis: from Epidemiology to Mechanisms Endocr. Rev., October 1, 2008; 29(6): 697 - 725. [Abstract] [Full Text] [PDF]

				H. Ikegami, T. Awata, E. Kawasaki, T. Kobayashi, T. Maruyama, K. Nakanishi, A. Shimada, S. Amemiya, Y. Kawabata, S. Kurihara, et al. The Association of CTLA4 Polymorphism with Type 1 Diabetes Is Concentrated in Patients Complicated with Autoimmune Thyroid Disease: A Multicenter Collaborative Study in Japan J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1087 - 1092. [Abstract] [Full Text] [PDF]

				B. Golden, L. Levin, Y. Ban, E. Concepcion, D. A. Greenberg, and Y. Tomer Genetic Analysis of Families with Autoimmune Diabetes and Thyroiditis: Evidence for Common and Unique Genes J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4904 - 4911. [Abstract] [Full Text] [PDF]

				F. K. Kavvoura and J. P. A. Ioannidis CTLA-4 Gene Polymorphisms and Susceptibility to Type 1 Diabetes Mellitus: A HuGE Review and Meta-Analysis Am. J. Epidemiol., July 1, 2005; 162(1): 3 - 16. [Abstract] [Full Text] [PDF]

				S. M. Anjos, M.-C. Tessier, and C. Polychronakos Association of the Cytotoxic T Lymphocyte-Associated Antigen 4 Gene with Type 1 Diabetes: Evidence for Independent Effects of Two Polymorphisms on the Same Haplotype Block J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6257 - 6265. [Abstract] [Full Text] [PDF]

				M. Mochizuki, S. Amemiya, K. Kobayashi, K. Kobayashi, Y. Shimura, T. Ishihara, Y. Nakagomi, K. Onigata, S. Tamai, A. Kasuga, et al. Association of the CTLA-4 Gene 49 A/G Polymorphism With Type 1 Diabetes and Autoimmune Thyroid Disease in Japanese Children Diabetes Care, March 1, 2003; 26(3): 843 - 847. [Abstract] [Full Text] [PDF]

				Y. Kinjo, N. Takasu, I. Komiya, T. Tomoyose, M. Takara, T. Kouki, Y. Shimajiri, K. Yabiku, and H. Yoshimura Remission of Graves' Hyperthyroidism and A/G Polymorphism at Position 49 in Exon 1 of Cytotoxic T Lymphocyte-Associated Molecule-4 Gene J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2593 - 2596. [Abstract] [Full Text] [PDF]