Association of variants m.T16172C and m.T16519C in whole mtDNA sequences with high altitude pulmonary edema in Han Chinese lowlanders

Background: High altitude pulmonary edema (HAPE) is a hypoxia-induced non-cardiogenic pulmonary edema that typically occurred in un-acclimatized lowlanders, which inevitably leads to life-threatening consequences. Apart from multiple factors involved, the genetic factors also play an important role in the pathogenesis of HAPE. So far, researchers put more energy into the nuclear genome and HAPE, and ignored the relationship between the mitochondrion DNA (mtDNA) variants and HAPE susceptibility. Methods: We recruited a total of 366 individuals including 181 HAPE patients and 185 healthy or non-HAPE populations through two times. The first time, 49 HAPE patients and 58 non-HAPE cases were performed through whole mtDNA sequences to search the mutations and haplogroups, which were associated with the HAPE. The second time, 132 HAPE patients and 127 non-HAPE subjects were collected to apply of verifying these variants and haplogroups of mtDNA with routine PCR method. Results: We analyzed and summarized the clinical characteristics and sequence data for 49 HAPE patients and 58 non-HAPE cases. We found that a series of routine blood indexes including systolic arterial blood pressure (SBP), heart rate (HR), white blood cell (WBC) and C-reactive protein (CRP) in HAPE group presented higher and displayed the significant differences compared with those in non-HAPE group. Though the average numbers of variants in different regions and groups samples were not statistically significant (P > 0.05), the mutation densities of different region in the internal group shown the significant differences. Then we found that two mutations (T16172C and T16519C) associated with the HAPE susceptibility, and the T16172C mutation increased the risk of HAPE, and the T16519C mutation decreased the HAPE rating. Furthermore, the two mutations were demonstrated with 132 HAPE cases and 127 non-HAPE individuals. Unfortunately, all the haplogroups were not associated with the HAPE haplogroups.Conclusions: We provided the evidence of differences in mtDNA polymorphism frequencies between HAPE and non-HAPE Han Chinese. Genotypes of mtDNA 16172C and 16519C were correlated with HAPE susceptibility, which indicated that the role in mitochondrial genome in the pathogenesis of HAPE.