Mitochondrial DNA association study of type 2 diabetes with or without ischemic stroke in Taiwan.
BACKGROUND
The importance of mitochondrial DNA (mtDNA) polymorphism in the prediction of type 2 diabetes (T2D) in men and women is not well understood. We questioned whether mtDNA polymorphism, mitochondrial functions, age and gender influenced the occurrence of T2D with or without ischemic stroke (IS).


METHODS
We first designed a matched case-control study of 373 T2D patients and 327 healthy unrelated individuals without history of IS. MtDNA haplogroups were determined on all participants using sequencing of the control region and relevant SNPs from the coding region. Mitochondria functional tests, systemic biochemical measurements and complete genomic mtDNA sequencing were further determined on 239 participants (73 healthy controls, 33 T2D with IS, 70 T2D only and 63 IS patients without T2D).


RESULTS
MtDNA haplogroups B4a1a, and E2b1 showed significant association with T2D (P <0.05), and haplogroup D4 indicated resistance (P <0.05). Mitochondrial and systemic functional tests showed significantly less variance within groups bearing the same mtDNA haplotypes. There was a pronounced male excess among all T2D patients and prevalence of IS was seen only in the older population. Finally, nucleotide variant np 15746, a determinant of haplogroup G3 seen in Japanese and of B4a1a prevalent in Taiwanese was associated with T2D in both populations.


CONCLUSIONS
Men appeared more susceptible to T2D than women. Although the significant association of B4a1a and E2b1 with T2D ceased when corrected for multiple testings, these haplogroups are seen only among Taiwan Aborigines, Southeast Asian and the Pacific Ocean islanders where T2D is predominant. The data further suggested that physiological and biochemical measurements were influenced by the mtDNA genetic profile of the individual. More understanding of the function of the mitochondrion in the development of T2D might indicate ways of influencing the early course of the disease.
Jun-Hun
JH
Loo
Jean A
JA
Trejaut
Ju-Chen
JC
Yen
Zong-Sian
ZS
Chen
Wai-Mei
WM
Ng
Chin-Yuan
CY
Huang
Kuang-Nan
KN
Hsu
Kuo-Hua
KH
Hung
Yachun
Y
Hsiao
Yau-Huei
YH
Wei
Mackay Memorial Hospital, No, 45, Mínshēng Rd, Danshui District, New Taipei City, Taiwan. marilin@ms2.mmh.org.tw.
Marie
M
Lin
D000367:Age Factors; D000368:Aged; D001483:Base Sequence; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D020521:Stroke / Q000150:complications / Q000235:genetics* / Q000473:pathology; D013624:Taiwan
D004272:DNA, Mitochondrial