Mitochondrial DNA Mutations Associated with Type 2 Diabetes Mellitus in Chinese Uyghur Population

Overview

Journal Sci Rep

Specialty Science

Date 2017 Dec 7

PMID 29208909

Citations 20

Authors

Wenxi Jiang

Ronghui Li

Yongbiao Zhang

Panpan Wang

Tingting Wu

Jinming Lin

Jun Yu

Mingliang Gu

Affiliations

Soon will be listed here.

Abstract

A hospital-based case-control study was conducted to investigate potential association between mitochondrial DNA and Type 2 diabetes mellitus (T2DM) in Chinese Uyghur population. We sequenced mitochondrial DNA from 210 Uyghur individuals including 88 T2DM patients and 122 controls. Using haplogroup classification and association test, we found that haplogroup H (odds ratio [OR] = 1.40; 95% confidence interval [CI]: 1.20-1.64; P = 0.0005138) and D4 (odds ratio = 1.47; 95% CI: 1.22-1.77; P = 0.001064) were associated with an increased risk of T2DM in Chinese Uyghur population. Two markers of haplogroup D4 and H, MT-ATP8 m.8414 T > G (p.Leu17Phe) and m.2706 G > A encoding 16S rRNA in mitochondria, were predicted to affect the structure of MT-ATP8 and 16S RNA, respectively, and may be involved in the pathogenesis of T2DM. Our study provides a new clue for mitochondrial DNA in the etiology of T2DM in Chinese Uyghur population.

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References

Tang H, Thomas P . PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation. Bioinformatics. 2016; 32(14):2230-2. DOI: 10.1093/bioinformatics/btw222. View

Larsen S, Diez-Sanchez C, Rabol R, Ara I, Dela F, Helge J . Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H. Biochim Biophys Acta. 2013; 1837(2):226-31. DOI: 10.1016/j.bbabio.2013.10.009. View

Roglic G, Unwin N . Mortality attributable to diabetes: estimates for the year 2010. Diabetes Res Clin Pract. 2009; 87(1):15-9. DOI: 10.1016/j.diabres.2009.10.006. View

Liou C, Chen J, Tiao M, Weng S, Huang T, Chuang J . Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes. Diabetes. 2012; 61(10):2642-51. PMC: 3447893. DOI: 10.2337/db11-1369. View

Festa A, Williams K, DAgostino Jr R, Wagenknecht L, Haffner S . The natural course of beta-cell function in nondiabetic and diabetic individuals: the Insulin Resistance Atherosclerosis Study. Diabetes. 2006; 55(4):1114-20. DOI: 10.2337/diabetes.55.04.06.db05-1100. View

Guo L, Oshida Y, Fuku N, Takeyasu T, Fujita Y, Kurata M . Mitochondrial genome polymorphisms associated with type-2 diabetes or obesity. Mitochondrion. 2005; 5(1):15-33. DOI: 10.1016/j.mito.2004.09.001. View

Christine P, Auchincloss A, Bertoni A, Carnethon M, Sanchez B, Moore K . Longitudinal Associations Between Neighborhood Physical and Social Environments and Incident Type 2 Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis (MESA). JAMA Intern Med. 2015; 175(8):1311-20. PMC: 4799846. DOI: 10.1001/jamainternmed.2015.2691. View

Blaszczyk M, Jamroz M, Kmiecik S, Kolinski A . CABS-fold: Server for the de novo and consensus-based prediction of protein structure. Nucleic Acids Res. 2013; 41(Web Server issue):W406-11. PMC: 3692050. DOI: 10.1093/nar/gkt462. View

Amunts A, Brown A, Toots J, Scheres S, Ramakrishnan V . Ribosome. The structure of the human mitochondrial ribosome. Science. 2015; 348(6230):95-98. PMC: 4501431. DOI: 10.1126/science.aaa1193. View

10.

Reuter J, Mathews D . RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics. 2010; 11:129. PMC: 2984261. DOI: 10.1186/1471-2105-11-129. View

11.

Zhang J, Zhang Z, Ding Y, Xu P, Wang T, Xu W . Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population. J Diabetes Res. 2015; 2015:905042. PMC: 4530283. DOI: 10.1155/2015/905042. View

12.

Soini H, Moilanen J, Finnila S, Majamaa K . Mitochondrial DNA sequence variation in Finnish patients with matrilineal diabetes mellitus. BMC Res Notes. 2012; 5:350. PMC: 3434112. DOI: 10.1186/1756-0500-5-350. View

13.

Bar-Yaacov D, Frumkin I, Yashiro Y, Chujo T, Ishigami Y, Chemla Y . Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates. PLoS Biol. 2016; 14(9):e1002557. PMC: 5025228. DOI: 10.1371/journal.pbio.1002557. View

14.

Niu Q, Zhang W, Wang H, Guan X, Lu J, Li W . Effects of mitochondrial haplogroup N9a on type 2 diabetes mellitus and its associated complications. Exp Ther Med. 2015; 10(5):1918-1924. PMC: 4665168. DOI: 10.3892/etm.2015.2751. View

15.

Fuku N, Park K, Yamada Y, Nishigaki Y, Cho Y, Matsuo H . Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians. Am J Hum Genet. 2007; 80(3):407-15. PMC: 1821119. DOI: 10.1086/512202. View

16.

Bonnard C, Durand A, Peyrol S, Chanseaume E, Chauvin M, Morio B . Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J Clin Invest. 2008; 118(2):789-800. PMC: 2176186. DOI: 10.1172/JCI32601. View

17.

Gordon J, Dolinsky V, Mughal W, Gordon G, McGavock J . Targeting skeletal muscle mitochondria to prevent type 2 diabetes in youth. Biochem Cell Biol. 2015; 93(5):452-65. DOI: 10.1139/bcb-2015-0012. View

18.

Adzhubei I, Schmidt S, Peshkin L, Ramensky V, Gerasimova A, Bork P . A method and server for predicting damaging missense mutations. Nat Methods. 2010; 7(4):248-9. PMC: 2855889. DOI: 10.1038/nmeth0410-248. View

19.

Santoro A, Balbi V, Balducci E, Pirazzini C, Rosini F, Tavano F . Evidence for sub-haplogroup h5 of mitochondrial DNA as a risk factor for late onset Alzheimer's disease. PLoS One. 2010; 5(8):e12037. PMC: 2917370. DOI: 10.1371/journal.pone.0012037. View

20.

Zimmet P, Alberti K, Shaw J . Global and societal implications of the diabetes epidemic. Nature. 2001; 414(6865):782-7. DOI: 10.1038/414782a. View