The prevalence of an interrupted poly-C tract variant harboring mitochondrial DNA haplogroup B and its association with reduced susceptibility to type 2 diabetes in Korea
- 127 Downloads
Recent reports suggest that the mitochondrial DNA (mtDNA) poly-C tract (16184–16193 polycytosine tract) variant and its relevant haplogroup lineages could be associated with type 2 diabetes mellitus (T2DM); however, subsequent surveys of this relationship have yielded conflicting results, some finding significant associations and others reporting no significant effect. Therefore, to assess the possible contribution of mtDNA haplogroup-specific variants to the occurrence of T2DM, we performed a population-based study on Korean diabetes cases and controls. The distribution of 16184–16193 poly-C tract variants and their relevant haplogroup B lineage were typed in the Korean population using APLP/PCR–RFLP/sequencing on a total of 497 T2DM cases and 500 corresponding controls. While the haplogroup B distribution of the T2DM cases did not differ significantly from the controls, the frequency of an interrupted poly-C tract with T16189C variation harboring mtDNA haplogroup B was significantly higher in controls compared to the T2DM patients (OR 0.106, 95 % CI 0.002–0.785, p = 0.012). Thus, our data imply that the specific mtDNA haplogroup B lineage retaining the interrupted poly-C tract is significantly associated with reduced susceptibility to T2DM in the Korean population, although functional studies with larger sample size from diverse regions of different ethnic populations are necessary to further substantiate these findings.
KeywordsMitochondrial DNA Haplogroup B Poly-C tract T16189C variant Type 2 diabetes Koreans
The biospecimens for this study were provided by National Biobank of Korea (KOBB-2012-1046). They also thank S.S. Hong for technical assistance during the course of this work. Comments and discussion on this manuscript by Chris Tyler-Smith (The Wellcome Trust) were also greatly appreciated. This work was supported by grants from National Research Foundation of Korea (NRF-2012R1A1A2041245) with additional support from National Forensic Service of Korea (2014). This work was also supported in part by DANKOOK ChemBio Specialization for Creative Korea-II (2014).
Compliance with ethical standards
The study was approved by the Ethics Committee and Institutional Review Board of Dankook University, Korea.
Conflict of interest
The authors declare no conflict of interest.
- Das S, Bennett AJ, Sovio U, Ruokonen A, Martikainen H, Pouta A, Hartikainen AL, Franks S, Elliott P, Poulton J et al (2007) Detailed analysis of variation at and around mitochondrial position 16189 in a large Finnish cohort reveals no significant associations with early growth or metabolic phenotypes at age 31 years. J Clin Endocrinol Metab 92:3219–3223CrossRefPubMedGoogle Scholar
- Kim JH, Park KS, Cho YM, Kang BS, Kim SK, Jeon HJ, Kim SY, Lee HK (2002) The prevalence of the mitochondrial DNA 16189 variant in non-diabetic Korean adults and its association with higher fasting glucose and body mass index. Diabet Med 19:681–684Google Scholar
- Liou CW, Lin TK, Huei Weng H, Lee CF, Chen TL, Wei YH, Chen SD, Chuang YC, Weng SW, Wang PW (2007) A common mitochondrial DNA variant and increased body mass index as associated factors for development of type 2 diabetes: additive effects of genetic and environmental factors. J Clin Endocrinol Metab 92:235–239CrossRefPubMedGoogle Scholar
- Umetsu K, Tanaka M, Yuasa I, Adachi N, Miyoshi A, Kashimura S, Park KS, Wei YH, Watanabe G, Osawa M (2005) Multiplex amplified product-length polymorphism analysis of 36 mitochondrial single-nucleotide polymorphisms for haplogrouping of East Asian populations. Electrophoresis 26:91–98CrossRefPubMedGoogle Scholar
- van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, van de Kamp JJ, Maassen JA (1992) Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet 1:368–371CrossRefPubMedGoogle Scholar