PMID- 29997041
OWN - NLM
STAT- MEDLINE
DCOM- 20181108
LR  - 20240213
IS  - 0005-2728 (Print)
IS  - 1879-2650 (Electronic)
IS  - 0005-2728 (Linking)
VI  - 1859
IP  - 9
DP  - 2018 Sep
TI  - Mitochondrial DNA associations with East Asian metabolic syndrome.
PG  - 878-892
LID - S0005-2728(18)30189-0 [pii]
LID - 10.1016/j.bbabio.2018.07.002 [doi]
AB  - Mitochondrial dysfunction has repeatedly been reported associated with type 2 
      diabetes mellitus (T2DM) and metabolic syndrome (MS), as have mitochondrial DNA 
      (mtDNA) tRNA and duplication mutations and mtDNA haplogroup lineages. We 
      identified 19 Taiwanese T2DM and MS pedigrees from Taiwan, with putative 
      matrilineal transmission, one of which harbored the pathogenic mtDNA 
      tRNA(Leu(UUR)) nucleotide (nt) 3243A>G mutation on the N9a3 haplogroup 
      background. We then recruited three independent Taiwanese cohorts, two from 
      Taipei (N = 498, mean age 52 and N = 1002, mean age 44) and one from a non-urban 
      environment (N = 501, mean age 57). All three cohorts were assessed for an array 
      of metabolic parameters, their mtDNA haplogroups determined, and the haplogroups 
      correlated with T2DM/MS phenotypes. Logistic regression analysis revealed that 
      mtDNA haplogroups D5, F4, and N9a conferred T2DM protection, while haplogroups F4 
      and N9a were risk factors for hypertension (HTN), and F4 was a risk factor for 
      obesity (OB). Additionally, the 5263C>T (ND2 A165V) variant commonly associated 
      with F4 was associated with hypertension (HTN). Cybrids were prepared with 
      macro-haplogroup N (defined by variants m.ND3 10398A (114T) and m.ATP6 8701A 
      (59T)) haplogroups B4 and F1 mtDNAs and from macro-haplogroup M (variants m.ND3 
      10398G (114A) and m.ATP6 8701G (59A)) haplogroup M9 mtDNAs. Additionally, 
      haplogroup B4 and F1 cybrids were prepared with and without the mtDNA variant in 
      ND1 3394T>C (Y30H) reported to be associated with T2DM. Assay of mitochondria 
      complex I in these cybrids revealed that macro-haplogroup N cybrids had lower 
      activity than M cybrids, that haplogroup F cybrids had lower activity than B4 
      cybrids, and that the ND1 3394T>C (Y30H) variant reduced complex I on both the B4 
      and F1 background but with very different cumulative effects. These data support 
      the hypothesis that functional mtDNA variants may contribute to the risk of 
      developing T2DM and MS.
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Chalkia, Dimitra
AU  - Chalkia D
AD  - Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA 19104, United States of America.
FAU - Chang, Yi-Cheng
AU  - Chang YC
AD  - Department of Internal Medicine, National Taiwan University Medical College, 
      Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, National 
      Taiwan University Medical College, Taipei, Taiwan; Institute of Biomedical 
      Science, Academia Sinica, Taipei, Taiwan.
FAU - Derbeneva, Olga
AU  - Derbeneva O
AD  - Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA 19104, United States of America; Department of 
      Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 
      19104, United States of America.
FAU - Lvova, Maria
AU  - Lvova M
AD  - Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA 19104, United States of America.
FAU - Wang, Ping
AU  - Wang P
AD  - Department of Medicine, University of California, Irvine School of Medicine, 
      Irvine, CA 92697, United States of America.
FAU - Mishmar, Dan
AU  - Mishmar D
AD  - Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 
      8410501, Israel.
FAU - Liu, Xiaogang
AU  - Liu X
AD  - Douglas C. Wallace Institute for Mitochondrial and Epigenomic Information 
      Sciences, The Key Laboratory of Biomedical Information Engineering of the 
      Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong 
      University, Xi'an, PR China; Institute of Molecular Genetics, School of Life 
      Science and Technology, Xi'an Jiaotong University, Xi'an, PR China.
FAU - Singh, Larry N
AU  - Singh LN
AD  - Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA 19104, United States of America.
FAU - Chuang, Lee-Ming
AU  - Chuang LM
AD  - Department of Internal Medicine, National Taiwan University Medical College, 
      Taipei, Taiwan.
FAU - Wallace, Douglas C
AU  - Wallace DC
AD  - Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA 19104, United States of America; Department of 
      Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 
      19104, United States of America; Douglas C. Wallace Institute for Mitochondrial 
      and Epigenomic Information Sciences, The Key Laboratory of Biomedical Information 
      Engineering of the Ministry of Education, School of Life Science and Technology, 
      Xi'an Jiaotong University, Xi'an, PR China; Institute of Molecular Genetics, 
      School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, PR 
      China. Electronic address: wallaced1@email.chop.edu.
LA  - eng
GR  - UL1 TR001414/NH/NIH HHS/United States
GR  - UL1 RR031985/RR/NCRR NIH HHS/United States
GR  - DK73691/NH/NIH HHS/United States
GR  - UL1 TR001414/TR/NCATS NIH HHS/United States
GR  - U54 HD086984/HD/NICHD NIH HHS/United States
GR  - R01 DK073691/DK/NIDDK NIH HHS/United States
GR  - R01 NS021328/NS/NINDS NIH HHS/United States
GR  - UL1 RR031985/NH/NIH HHS/United States
GR  - NS021328/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180708
PL  - Netherlands
TA  - Biochim Biophys Acta Bioenerg
JT  - Biochimica et biophysica acta. Bioenergetics
JID - 101731706
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - Adult
MH  - Asian People/*genetics
MH  - Case-Control Studies
MH  - DNA, Mitochondrial/*genetics
MH  - Diabetes Mellitus, Type 2/epidemiology/*genetics
MH  - Asia, Eastern/epidemiology
MH  - Female
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Metabolic Syndrome/epidemiology/*genetics
MH  - Middle Aged
MH  - Mitochondria/metabolism/*pathology
MH  - Pedigree
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
PMC - PMC6530988
MID - NIHMS1014168
OTO - NOTNLM
OT  - Cybrids
OT  - Diabetes
OT  - Haplogroup
OT  - Mitochondria
OT  - Obesity
OT  - mtDNA
EDAT- 2018/07/13 06:00
MHDA- 2018/11/09 06:00
PMCR- 2019/09/01
CRDT- 2018/07/13 06:00
PHST- 2018/04/18 00:00 [received]
PHST- 2018/07/04 00:00 [revised]
PHST- 2018/07/04 00:00 [accepted]
PHST- 2018/07/13 06:00 [pubmed]
PHST- 2018/11/09 06:00 [medline]
PHST- 2018/07/13 06:00 [entrez]
PHST- 2019/09/01 00:00 [pmc-release]
AID - S0005-2728(18)30189-0 [pii]
AID - 10.1016/j.bbabio.2018.07.002 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Bioenerg. 2018 Sep;1859(9):878-892. doi: 
      10.1016/j.bbabio.2018.07.002. Epub 2018 Jul 8.