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A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians

Cited 76 time in Web of Science Cited 81 time in Scopus
Authors
Park, K. S.; Chan, J. C.; Chuang, L-M.; Suzuki, S.; Araki, E.; Nanjo, K.; Ji, L.; Ng, M.; Nishi, M.; Furuta, H.; Shirotani, T.; Ahn, B. Y.; Chung, S. S.; Min, H-K.; Lee, S. W.; Kim, J. H.; Cho, Y. M.; Lee, H. K.
Issue Date
2008-02-06
Publisher
Springer Verlag
Citation
Diabetologia. 2008 ;51(4):602-8.
Keywords
Asian Continental Ancestry Group/geneticsChinaDNA PrimersDNA, Mitochondrial/*geneticsDiabetes Mellitus, Type 2/epidemiology/*genetics*Genetic VariationHumansJapanKorea*Polymorphism, Single NucleotideTaiwan
Abstract
AIMS/HYPOTHESIS: This multinational study was conducted to investigate the association between a mitochondrial DNA (mtDNA) T16189C polymorphism and type 2 diabetes in Asians. The mtDNA 16189C variant has been reported to be associated with insulin resistance and type 2 diabetes. However, a recent meta-analysis concluded that it is negatively associated with type 2 diabetes in Europids. Since the phenotype of an mtDNA mutant may be influenced by environmental factors and ethnic differences in the nuclear and mitochondrial genomes, we investigated the association between the 16189C variant and type 2 diabetes in Asians. METHODS: The presence of the mtDNA 16189C variant was determined in 2,469 patients with type 2 diabetes and 1,205 non-diabetic individuals from Korea, Japan, Taiwan, Hong Kong and China. An additional meta-analysis including previously published Asian studies was performed. Since mtDNA nucleotide position 16189 is very close to the mtDNA origin of replication, we performed DNA-linked affinity chromatography and reverse-phase liquid chromatography/tandem mass spectrometry and chromatin immunoprecipitation to identify protein bound to the 16189 region. RESULTS: Analysis of participants from five Asian countries confirmed the association between the 16189C variant and type 2 diabetes [odds ratio (OR) 1.256, 95% CI 1.08-1.46, p=0.003]. Inclusion of data from three previously published Asian studies (type 2 diabetes n=3,283, controls n=2,176) in a meta-analysis showed similar results (OR 1.335, 95% CI 1.18-1.51, p=0.000003). Mitochondrial single-stranded DNA-binding protein (mtSSB) was identified as a candidate protein bound to the 16189 region. Chromatin immunoprecipitation in cybrid cells showed that mtSSB has a lower binding affinity for the 16189C variant than the wild-type sequence. CONCLUSIONS/INTERPRETATION: The mtDNA 16189C variant is associated with an increased risk of type 2 diabetes in Asians.
ISSN
0012-186X (Print)
Language
English
URI
http://hdl.handle.net/10371/62189
DOI
https://doi.org/10.1007/s00125-008-0933-z
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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