Dr. Chang, Yi-Cheng
Joint Appointment Assistant Research Fellow
- 02-23123456 ext 88656 (NTU) (Lab) (Room No: 343)
- 02-33936523 (Fax)
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Specialty:
- Diabetes and Obesity
- Genetic epidemiology
Education and Positions:
Education:
M.D. -National Taiwan University
Ph.D. -Academia Sinica and National Taiwan University Joint Ph.D. Program of Translational Medicine
Position:
- Associate Professor, Graduate Institute of Medical Genomics and Proteomics, Medical College, National Taiwan University
- Attending Physician, Department of Endocrinology and Metabolism, National Taiwan University Hospital
- Vice CEO, Center for Bariatric and Metabolic Surgery, National Taiwan University Hospital
Highlight Detail
Mitochondrial DNA associations with East Asian metabolic syndrome
Dr. Chang, Yi-Cheng
Biochimica et Biophysica Acta (BBA) - Bioenergetics, Sep 01, 2018Mitochondrial 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 identi fi ed 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 (de fi ned 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 di ff erent cumulative e ff ects. These data support the hypothesis that functional mtDNA variants may contribute to the risk of developing T2DM and MS.