Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes.
Both the coding and control regions of mitochondrial DNA (mtDNA) play roles in the generation of diabetes; however, no studies have thoroughly reported on the combined diabetogenic effects of variants in the two regions. We determined the mitochondrial haplogroup and the mtDNA sequence of the control region in 859 subjects with diabetes and 1,151 normoglycemic control subjects. Full-length mtDNA sequences were conducted in 40 subjects harboring specific diabetes-related haplogroups. Multivariate logistic regression analysis with adjustment for age, sex, and BMI revealed that subjects harboring the mitochondrial haplogroup B4 have significant association with diabetes (DM) (odds ratio [OR], 1.54 [95% CI 1.18-2.02]; P < 0.001), whereas subjects harboring D4 have borderline resistance against DM generation (0.68 [0.49-0.94]; P = 0.02). Upon further study, we identified an mtDNA composite group susceptible to DM generation consisting of a 10398A allele at the coding region and a polycytosine variant at nucleotide pair 16184-16193 of the control region, as well as a resistant group consisting of C5178A, A10398G, and T152C variants. The OR for susceptible group is 1.31 (95% CI 1.04-1.67; P = 0.024) and for the resistant group is 0.48 (0.31-0.75; P = 0.001). Our study found that mtDNA variants in the coding and control regions can have combined effects influencing diabetes generation.
Department of Neurology, Mitochondrial Research Unit, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chia-Wei
CW
Liou
Jin-Bor
JB
Chen
Mao-Meng
MM
Tiao
Shao-Wen
SW
Weng
Tiao-Lai
TL
Huang
Jiin-Haur
JH
Chuang
Shang-Der
SD
Chen
Yao-Chung
YC
Chuang
Wen-Chin
WC
Lee
Tsu-Kung
TK
Lin
Pei-Wen
PW
Wang
D000328:Adult; D044466:Asian People / Q000235:genetics; D004272:DNA, Mitochondrial; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D013624:Taiwan
D004272:DNA, Mitochondrial