Mitochondrial DNA 10609T promotes hypoxia-induced increase of intracellular ROS and is a risk factor of high altitude polycythemia.
Hypobaric hypoxia is the primary cause of high altitude polycythemia (HAPC). Mitochondria are critical organelles that consume high levels of oxygen and generate ATP. We hypothesize that the mitochondrion may be at the center of HAPC, and mitochondrial DNA (mtDNA) SNPs may be involved in its development. First, we conducted a case-control study to investigate the association of mtDNA variants with HAPC in Han Chinese migrating to the Qinghai-Tibetan Plateau. Pearson's chi-square tests revealed that mtDNA 8414T (MU) frequency (19.5%) in the HAPC group was significantly higher than that of the control (13.0%, P = 0.04, OR = 1.615, 95%CI: 1.020-2.555). The multivariate logistic regression analysis, after adjustment for environmental factors, revealed that mtDNA 10609T (WT) was significantly associated with an increased risk of HAPC (P<0.01, OR = 2.558, 95%CI: 1.250-5.236). Second, to verify the association, in vitro experiments of transmitochondrial cybrids was performed and revealed that the mtDNA 10609 variant promoted hypoxia-induced increase of intracellular ROS, but the mtDNA 8414 variant did not. Our findings provide evidence that, in Han Chinese, mtDNA 10609T promotes hypoxia-induced increase of intracellular ROS and is a HAPC risk factor.
Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, PLA, Chongqing, PR China.
Chunhua
C
Jiang
Research Center of PLA for Prevention and Treatment of High Mountain Sickness, the 18th Hospital of PLA, Yecheng, Xinjiang, PR China.
Jianhua
J
Cui
Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, PLA, Chongqing, PR China.
Fuyu
F
Liu
Research Center of PLA for Prevention and Treatment of High Mountain Sickness, the 18th Hospital of PLA, Yecheng, Xinjiang, PR China.
Liang
L
Gao
Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, PLA, Chongqing, PR China.
Yongjun
Y
Luo
Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, PLA, Chongqing, PR China.
Peng
P
Li
Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, PLA, Chongqing, PR China.
Libin
L
Guan
Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, PR China ; Key Laboratory of High Altitude Medicine, PLA, Chongqing, PR China.
Yuqi
Y
Gao
D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D011086:Polycythemia / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species