Rare Mitochondrial DNA Polymorphisms are Associated with High Altitude Pulmonary Edema (HAPE) Susceptibility in Han Chinese

Abstract

Background.— The role of genetics in determining an individual's susceptibility to high altitude pulmonary edema (HAPE) is unclear. However a number of genetic polymorphisms have recently been found to be overrepresented in patients with HAPE. Changes at the mitochondrial level may play an important role in the human body's adaptation to hypoxia. Polymorphisms of mitochondrial DNA (mtDNA) have been shown to be responsible for differences in organelle function. Therefore, the frequency of mtDNA 3397A/G and 3552T/A polymorphisms were studied to determine their potential role in HAPE. Objectives.— To further study the role of mtDNA 3397A/G and 3552T/A variations of reduced nicotinamide adenosine dinucleotide dehydrogenase 1 in HAPE susceptibility. Methods.— The single-nucleotide polymorphisms of mtDNA 3397 and 3552 in patients with HAPE ( n = 132) and their matched control subjects ( n = 233) were studied using polymerase chain reaction sequencing. Results.— The frequency of mtDNA 3397G in the HAPE group (2.3%) was significantly higher than that of the control group (0%; P = .021; odds ratio, 2.806; 95% confidence interval, 2.443 to 3.223). The frequency of mtDNA 3552A in the HAPE group (6.8%) also was significantly higher than in the control group (1.7%; P = .012; odds ratio, 4.198; 95% confidence interval, 1.264 to 13.880). Conclusions.— In this study, we present the first evidence of differences in mtDNA polymorphism frequencies between HAPE victims and healthy Han Chinese. Genotypes of mtDNA 3397G and 3552A were correlated with HAPE susceptibility. This result could contribute to defining the role of the mitochondrial genome in the pathogenesis of HAPE.

Metabolite Modulation in Human Plasma in the Early Phase of Acclimatization to Hypobaric Hypoxia

“…Our previous studies showed mitochondrial gene polymorphisms are also involved in the processes of acute impairment and chronic acclimatization of migrating lowlanders, as well as genetic adaptation of native residents at high altitudes 44 . Some individuals with certain mitochondrial DNA variations are susceptible to mountain sicknesses 45 . However, specific tests or biomarkers are sought after which would be more reliable and accessible for early prediction of AMS-S.…”

Mitochondrial DNA sequencing reveals association of variants and haplogroup M33a2′3 with High altitude pulmonary edema susceptibility in Indian male lowlanders

“…High altitude Pulmonary Edema (HAPE) is a life threatening, multifactorial complex disease condition which occurs due to rapid ascent to high altitude ~ 3000 m above sea level, where the oxygen content in air is only 60% of that at sea level 7 . Genetic predisposition to the disease is largely unknown, but it would be a function of gene environment interaction 8 . The role of genetics in determining the individual’s susceptibility to HAPE is unclear.…”

“…Studies also showed that certain mitochondrial haplogroups are predisposed to high-altitude diseases while others can protect against mountain sickness 17,18 . Research on mitochondrial genome shows that haplotype 3010G–3970C is significantly different in frequency between high and low altitude populations suggesting that this haplotype may be responsible for adaptation to low-oxygen environment 19 . Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese men 20 .…”

High Altitude Pulmonary Edema in an Experienced Mountaineer. Possible Genetic Predisposition

“… 6 , 7 It is believed that the renin-angiotensin-aldosterone system, nitric oxide pathway, and hypoxia-inducible factor pathway, are controlled by genes that differ in HAPE-susceptible patients. 6 Other studies provide evidence of mitochondrial DNA 8 or heat shock protein 9 polymorphisms in HAPE-susceptible individuals or differences within the major histocompatibility complex. 10 Although the genetic connection is not yet clearly established by the research, these and future studies may help to better explain our patient’s risk, protecting his offspring in future generations.…”