HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Ohkubo, K. Articles by Ono, J. Search for Related Content PubMed PubMed Citation Articles by Ohkubo, K. Articles by Ono, J. Related Collections Molecular Diagnostics and Genetics Endocrinology and Metabolism

Mitochondrial Gene Mutations in the tRNA^Leu(UUR) Region and Diabetes: Prevalence and Clinical Phenotypes in Japan

¹ Department of Laboratory Medicine, Fukuoka University School of Medicine, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

² The First Department of Internal Medicine, Fukuoka University School of Medicine, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

³ Kyushu Clinical Pharmacology Research Clinic, 2-13-16, Jigyo, Chuo-ku, Fukuoka, 810-0065, Japan.

^aAuthor for correspondence. Fax 81-92-873-1050; e-mail kokubo{at}cis.fukuoka-u.ac.jp.

Background: Mitochondrial gene mutations play a role in the development of diabetes mellitus. We have assessed the frequency of the A3243G and other mitochondrial mutations in Japan and in the relationship to clinical features of diabetes.

Methods: DNA was obtained from peripheral leukocytes of 240 patients with diabetes mellitus (39 with type 1; 188 with type 2; 13 with gestational diabetes) and 125 control subjects. We used PCR-restriction fragment length polymorphism analysis (ApaI) for A3243G and PCR-single-strand conformation polymorphism analysis to determine the mutations in the mitochondrial gene including nucleotide position 3243.

Results: The A3243G mutation was found in seven patients, and an inverse relationship was observed between the degree of heteroplasmy and the age at onset of diabetes. A3156G, G3357A, C3375A, and T3394C were detected in addition. Those who shared the same mutation showed similar clinical characteristics, thus representing a putative clinical subtype. The patients with A3156G had a sudden onset of hyperglycemia and showed a rapid progression to an insulin-dependent state with positive anti-glutamic acid decarboxylase antibody. Those with T3394C showed a mild defect in glucose-stimulated insulin secretion, and hyperglycemia appeared after adding such factors as aging or obesity.

Conclusions: The identification of mitochondrial gene mutations allows preclinical diagnosis of diabetes and prediction of the age at onset by evaluating the degree of heteroplasmy in cases with A3243G. Mutation detection may also be important for patient management and identification of affected family members.

The following articles in journals at HighWire Press have cited this article:

				M. Laloi-Michelin, T. Meas, C. Ambonville, C. Bellanne-Chantelot, S. Beaufils, P. Massin, B. Vialettes, H. Gin, J. Timsit, B. Bauduceau, et al. The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes J. Clin. Endocrinol. Metab., August 1, 2009; 94(8): 3025 - 3030. [Abstract] [Full Text] [PDF]

				M. R. R Gasparin, F. Crispim, S. L Paula, M. B. S Freire, I. S Dalbosco, T. D. Manna, J. E. N Salles, F. Gasparin, A. Guedes, J. M Marcantonio, et al. Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome Eur. J. Endocrinol., February 1, 2009; 160(2): 309 - 316. [Abstract] [Full Text] [PDF]

				R. P. Sahu, A. Aggarwal, G. Zaidi, A. Shah, K. Modi, S. Kongara, S. Aggarwal, S. Talwar, S. Chu, V. Bhatia, et al. Etiology of Early-Onset Type 2 Diabetes in Indians: Islet Autoimmunity and Mutations in Hepatocyte Nuclear Factor 1{alpha} and Mitochondrial Gene J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2462 - 2467. [Abstract] [Full Text] [PDF]

				Q.-P. Kong, H.-J. Bandelt, C. Sun, Y.-G. Yao, A. Salas, A. Achilli, C.-Y. Wang, L. Zhong, C.-L. Zhu, S.-F. Wu, et al. Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations Hum. Mol. Genet., July 1, 2006; 15(13): 2076 - 2086. [Abstract] [Full Text] [PDF]

				R.-K. Bai and L.-J. C. Wong Simultaneous Detection and Quantification of Mitochondrial DNA Deletion(s), Depletion, and Over-Replication in Patients with Mitochondrial Disease J. Mol. Diagn., November 1, 2005; 7(5): 613 - 622. [Abstract] [Full Text] [PDF]

				R.-K. Bai and L.-J. C. Wong Detection and Quantification of Heteroplasmic Mutant Mitochondrial DNA by Real-Time Amplification Refractory Mutation System Quantitative PCR Analysis: A Single-Step Approach Clin. Chem., June 1, 2004; 50(6): 996 - 1001. [Abstract] [Full Text] [PDF]

				J. A. Maassen, Leen. M. 't Hart, E. van Essen, R. J. Heine, G. Nijpels, R. S. Jahangir Tafrechi, A. K. Raap, G. M.C. Janssen, and H. H.P.J. Lemkes Mitochondrial Diabetes: Molecular Mechanisms and Clinical Presentation Diabetes, February 1, 2004; 53(90001): S103 - 109. [Abstract] [Full Text]

				Y. Gu, C. Wang, C. M. Roifman, and A. Cohen Role of MHC Class I in Immune Surveillance of Mitochondrial DNA Integrity J. Immunol., April 1, 2003; 170(7): 3603 - 3607. [Abstract] [Full Text] [PDF]