CN111676283A

CN111676283A - Application of mitochondrial DNA single nucleotide polymorphism related to occurrence of high altitude pulmonary edema

Info

Publication number: CN111676283A
Application number: CN202010424420.8A
Authority: CN
Inventors: 王艳; 封志纯
Original assignee: 7th Medical Center of PLA General Hospital
Current assignee: 7th Medical Center of PLA General Hospital
Priority date: 2020-05-19
Filing date: 2020-05-19
Publication date: 2020-09-18
Anticipated expiration: 2040-05-19
Also published as: CN111676283B

Abstract

The invention discloses application of mitochondrial DNA single nucleotide polymorphism related to occurrence of high altitude pulmonary edema. The invention provides a technical scheme for detecting the polymorphism or genotype (namely allele) of rs2853817 in human genome mitochondrial DNA and application of a substance in preparing a product for detecting the single nucleotide polymorphism related to high altitude pulmonary edema. The product for screening the patients with high altitude pulmonary edema can be prepared by combining the substance for detecting the polymorphism or genotype (i.e. allele) of rs2853817 with other substances (e.g. substances for detecting other single nucleotide polymorphisms or genotypes (i.e. alleles) related to high altitude pulmonary edema).

Description

Application of mitochondrial DNA single nucleotide polymorphism related to occurrence of high altitude pulmonary edema

Technical Field

The invention relates to application of mitochondrial DNA single nucleotide polymorphism related to occurrence of high altitude pulmonary edema in the field of individual susceptibility detection in population prevention of the occurrence of high altitude pulmonary edema.

Background

High Altitude Pulmonary Edema (HAPE) is the most common acute severe altitude disease in the plateau region, and if the treatment is not timely carried out, the life of the patient is endangered, and the problem is also a big problem which troubles the highland combat troops of various countries. In recent years, a series of studies have been made on the pathogenesis of HAPE at home and abroad, and unfortunately, the pathogenesis is still unclear, and the possible mechanisms which are currently accepted more generally are: on the one hand, the pulmonary vessels and alveolar respiratory epithelium of sensitive individuals have some important functional defects due to congenital genetic or acquired factors, and may cause excessive hypoxic pulmonary hypertension upon acute hypoxic exposure, which is the most critical link in HAPE development. On the other hand, impairment of the body's ability to clear the alveolar fluid due to genetic defects and impaired sodium transport from hypoxia to the alveolar epithelium may be a non-negligible important aspect of the promotion of HAPE.

It is well known that the most effective treatment for HAPE patients is oxygen inhalation and transport in plain areas, indicating that HAPE is a disease very sensitive to oxygen/energy metabolism changes, which may be the initiating factor and key link in the development of HAPE due to high altitude hypoxia. The main factor of the plateau environment affecting the body is oxygen deficiency, and the habit of the body on the plateau environment is mainly carried out around the oxygen intake-transportation-using axis. Mitochondria are the center of energy metabolism of the body, are the key place for using oxygen by tissues and cells, and more than 90 percent of energy consumption of the body comes from the oxidative phosphorylation of mitochondria. Therefore, mitochondria are very important as a "power plant" for cells in hypoxic cell injury and tissue, cell habituation to hypoxic environments. Currently, research on mitochondrial adaptation is a focus and focus of high altitude medical research.

The organism mitochondria contain a plurality of genetic materials, namely mitochondrial DNA (mtDNA), and the mtDNA is an extracellular circular double-stranded DNA molecule and consists of an inner light chain (L) and an outer heavy chain (H). The total length of human mtDNA is 16,569bp, and the mtDNA consists of a coding region and a non-coding region, wherein the coding region has the functions of coding 13 polypeptides related to oxidative phosphorylation, 2 groups of rRNA and 22 tRNAs. Because mtDNA has no intron, and mtDNA is expressed as maternal inheritance, and no histone is combined to protect the coding process, the mtDNA is easy to mutate, and can influence the genetic information carried by some important segments in a genome, and finally, diseases are caused.

The single nucleotide polymorphism (rs2853817) of mitochondrial DNA T16172C is a SNP site on human mitochondrial DNA, and the variation is a transition (T/C, A/G on its complementary strand). rs2853817 is located at MT: 16172(GRCh38), HGVS: NC-012920.1: m.16172T > C, located within the MT-D-loop gene.

Disclosure of Invention

The invention aims to solve the technical problem of how to screen individuals susceptible to high altitude pulmonary edema or predict susceptibility of people to high altitude pulmonary edema or screen individuals carrying genes susceptible to high altitude pulmonary edema or evaluate the risk of high altitude pulmonary edema.

In order to solve the technical problems, the invention firstly provides the following products of any one of the applications A1-A5 and A6:

A1. the application of the substance for detecting the polymorphism or genotype (namely allele) of rs2853817 in the human genome in the preparation of products for screening or assisting in screening susceptible individuals or non-susceptible individuals with high altitude pulmonary edema.

A2. The application of the substance for detecting the polymorphism or genotype (namely allele) of rs2853817 in human genome in the preparation of products for detecting or assisting in detecting the susceptibility of high altitude pulmonary edema.

A3. The application of the substance for detecting the polymorphism or genotype (namely allele) of rs2853817 in human genome in the preparation of products for detecting or assisting in detecting the risk of the high altitude pulmonary edema.

A4. The application of the substance for detecting the polymorphism or genotype (namely allele) of rs2853817 in human genome in the preparation of products for evaluating or assisting in evaluating the risk of the high altitude pulmonary edema.

A5. The application of the substance for detecting the polymorphism or genotype (namely allele) of rs2853817 in human genome in preparing products for screening or assisting in screening the susceptible genotype or non-susceptible genotype of high altitude pulmonary edema.

A6. A product containing a substance for detecting the polymorphism or genotype (i.e., allele) of rs2853817 in the human genome, which is any one of a) to d):

a) detecting a single nucleotide polymorphism or genotype product associated with high altitude pulmonary edema;

b) identifying or aiding in identifying a product of a single nucleotide polymorphism or genotype associated with high altitude pulmonary edema;

c) screening or assisting in screening products for patients with high altitude pulmonary edema;

d) detecting or assisting in detecting a product susceptible to high altitude pulmonary edema.

In the above applications and products, the detecting of the rs2853817 polymorphism or genotype in the human genome mitochondrial DNA may specifically be detecting of the rs2853817 nucleotide species. The polymorphism or genotype of rs2853817 is T or C. The T is the genotype with the locus rs2853817 as T, and the C is the genotype with the locus rs2853817 as C. The risk of suffering from high altitude pulmonary edema of the individual with the rs2853817 polymorphism or genotype C is higher than or is candidate to be higher than that of the individual with the rs2853817 polymorphism or genotype T.

In the above applications and products, the products are suitable for Chinese, such as Chinese in plain areas. The Chinese people can be Han nationality people, and the gender can be male.

In the above applications and products, the substance for detecting the rs2853817 polymorphism or genotype (i.e., allele) in the human genomic mitochondrial DNA may be a reagent and/or an instrument required for determining the rs2853817 polymorphism or genotype by at least one of the following methods: DNA sequencing, restriction enzyme fragment length polymorphism, single-strand conformation polymorphism, denaturing high performance liquid chromatography and SNP chip. The SNP chip comprises a chip based on nucleic acid hybridization reaction, a chip based on single base extension reaction, a chip based on allele-specific primer extension reaction, a chip based on one-step reaction, a chip based on primer connection reaction, a chip based on restriction enzyme reaction, a chip based on protein DNA binding reaction and a chip based on fluorescent molecule DNA binding reaction.

In the above applications and products, the substance for detecting the polymorphism or genotype of rs2853817 in the mitochondrial DNA of the human genome may contain a PCR primer and/or a single base extension primer for amplifying a DNA fragment of the human genome including rs 2853817.

The sequence of the PCR primer has no special requirement, as long as the genomic DNA fragment including rs2853817 can be amplified, for example, the PCR primer can be a primer pair composed of single-stranded DNAs shown as a sequence 1 and a sequence 2 in a sequence table, or the PCR primer can also be a primer pair composed of single-stranded DNAs shown as a sequence 4 and a sequence 5 in the sequence table. The single base extension primer can be designed according to the upstream or downstream (excluding the SNP site) of rs2853817 in a human genome, the extended nucleotide of the single base extension primer corresponds to the nucleotide of the rs2853817 site of the human genome, namely, the 3' terminal nucleotide of the single base extension primer corresponds to the adjacent nucleotide of the rs2853817 of the human genome (namely, the former nucleotide of the rs2853817 or the latter nucleotide of the rs2853817), and the single base extension primer can be a single-stranded DNA shown as a sequence 3 in a sequence table.

In the above applications and products, the product may be a reagent or a kit or a system, and the system may include a combination of a reagent or a kit and an apparatus, such as a product consisting of a PCR primer, a single base extension primer and a mass spectrometer, a combination of a PCR primer and a DNA sequencer, and a combination of a PCR reagent and a DNA sequencing reagent and a DNA sequencer. The product can comprise the substance for detecting the polymorphism or the genotype of the rs2853817 in the mitochondrial DNA of the human genome.

In one embodiment of the invention, a genome DNA segment including mitochondrial DNA rs2853817 is amplified by using a PCR primer, a single base extension reaction is performed by using an obtained PCR amplification product as a template, a sequence of the obtained extension product is detected, and polymorphism and genotype of rs2853817 are determined.

Experiments prove that in a case population consisting of 49 Chinese male Han nationality plateau pulmonary edema patients irrelevant to the blood margin of the plain region and a control population consisting of 58 Chinese male Han nationality normal people irrelevant to the blood margin of the plain region, the distribution frequency of the rs2853817 polymorphic site of mitochondrial DNA (the gene type C) in the case group is obviously higher than that in the control group (p-value is 0.016, df is 1). Genotype C was found to increase the probability of high altitude pulmonary edema, corrected by Logistic regression analysis (OR 4.701; 95% CI, 1.214-18.204; p-adjust ═ 0.035). The mitochondrial DNA rs2853817 is the single nucleotide polymorphism related to the high altitude pulmonary edema, the risk of HAPE occurrence of the population carrying the C allele at the T16172C (rs2853817) site is obviously higher than that of the population carrying the T allele at the T16172C (rs2853817) site, and the rs2853817 can be used for screening individuals susceptible to the high altitude pulmonary edema, predicting the susceptibility of the human to the high altitude pulmonary edema, screening individuals carrying the genes susceptible to the high altitude pulmonary edema and evaluating the risk of the high altitude pulmonary edema. In practical application, in order to improve the accuracy, the substance for detecting the rs2853817 polymorphism and genotype and other substances (such as substances for detecting other single nucleotide polymorphisms or genotypes related to the high altitude pulmonary edema) can be combined together to prepare a product for screening the individuals susceptible to the high altitude pulmonary edema.

Detailed Description

The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention. The examples provided below serve as a guide for further modifications by a person skilled in the art and do not constitute a limitation of the invention in any way.

The experimental procedures in the following examples are conventional unless otherwise specified.

Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

Example 1 establishment of a method for detecting genotype at site rs2853817 of mitochondrial DNA

rs2853817 is a SNP site on human mitochondrial DNA, and the mutation is a switch (T/C, A/G on its complementary strand). rs2853817 is located at MT: 16172(GRCh38), HGVS: NC-012920.1: m.16172T > C, located in MT-D-loop gene (NCBI Reference Sequence: NC-012920.1, 31-OCT-2014). The rs2853817 genotype is T or C. Wherein T is the genotype with the locus rs2853817 as T, and C is the genotype with the locus rs2853817 as C.

1. Extraction of genomic DNA

Extracting the genome DNA of a sample to be detected, and carrying out genotype detection by taking the genome DNA as a template.

2. Design and Synthesis of primers

The PCR amplification primers and single-base extension primers of rs2853817 were designed using Sequenom Genotyping Tools and MassARRAY Assay Design software, and were synthesized by bio-corporation. The sequence of the PCR amplification specific primer pair for detecting the rs2853817 site genotype of the mitochondrial DNA gene is as follows: a forward primer: 5'-ACGTTGGATGCAGCCACCATGAATATTGTACG-3' (SEQ ID NO: 1 in the sequence Listing); reverse primer: 5'-ACGTTGGATGGTACTTGCTTGTAAGCATGGG-3' (SEQ ID NO: 2 of the sequence Listing). The sequence of the single-base extension primer used for the single-base amplification reaction is 5'-CCTGTAGTACATAAAAACCCAA-3' (sequence 3 in the sequence listing)

3. Establishment of method for detecting genotype of mitochondrial DNA rs28538174 locus

3.1PCR amplification

PCR amplification was performed in 384-well plates, and the total volume of each reaction system, excluding the template, was 4. mu.L, and PCR reaction systems were prepared as shown in Table 1.

TABLE 1 Components of each PCR reaction System

Reagent	Volume (μ L)
		10 × PCR buffer	0.5
MgCl₂(25mM)	0.4
		dNTP mix(25mM)	0.1
HotStar Taq enzyme (5U/. mu.L)	0.1
		Ultrapure water	1.9
DNA shown in sequence 1	0.5
		Shown in sequence 2DNA	0.5
Total volume	4

The genomic DNA sample prepared in 1 above was removed, and the sample addition volume was adjusted to 1. mu.L, and each 5. mu.L PCR reaction system contained 20 to 50ng of template DNA, 0.5U of Hotstar Tag, 0.5pmol of each amplification primer, and 0.1. mu.L of 25mM dNTPs.

The PCR reaction program is: 4 minutes at 94 ℃; 94 ℃ for 20 seconds, 56 ℃ for 30 seconds, 72 ℃ for 1 minute, 45 cycles; 3 minutes at 72 ℃; keeping at 4 ℃.

Obtaining PCR products.

3.2 alkaline phosphatase treatment of PCR products

After completion of the PCR reaction, the PCR product obtained in 3.1 above was treated with SAP (shrimp alkaline phosphatase) to remove free dNTPs from the system, and an SAP reaction system was prepared as shown in Table 2.

TABLE 2 SAP reaction System

Reagent	Volume (μ L)
		Ultrapure water	1.53
10 × SAP buffer	0.17
		SAP enzyme (1.7U/ul)	0.3
PCR product	5
		Total volume	7

The reaction conditions are as follows: 40 minutes at 37 ℃; 5 minutes at 85 ℃; maintaining the temperature at 4 ℃.

The alkaline phosphatase-treated product was obtained.

3.3 Single base extension

After the alkaline phosphatase treatment, the single-base extension reaction was carried out, and a single-base extension reaction system was prepared as shown in Table 3.

TABLE 3 Single-base extension reaction System

Reagent	For each reaction, μ L
		Water (W)	1.53
10 × buffer for single-base extension reaction	0.17
		Single base extension reaction enzyme (1.7U/ul)	0.3
Alkaline phosphatase treated product	7
		DNA molecule shown in sequence 3	1
Total volume	10

The reaction conditions are as follows:

i.94 ℃ for 30 seconds

II.94 ℃ for 5 seconds

III.52 ℃ for 5 seconds

IV.80 ℃ for 5 seconds

V. Return to III, 4 cycles

VI, Return to II, 39 cycles

VII.72 ℃ for 3 minutes

VIII.4℃

Obtaining the single base extension product.

3.4 resin purification

Clean Resin (Sequenom, USA) was spread into a 6mg Resin plate; adding 16 μ l of water to the corresponding well of the single base extension product obtained in 3.3 above; pouring the dried resin into an extension product plate, sealing the film, and vertically rotating at a low speed for 30 minutes to ensure that the resin is fully contacted with reactants; the resin was allowed to settle to the bottom of the well by centrifugation to give a resin purified extension product.

3.5 chip spotting

The MassARRAY Nanodispenser RS1000 Spotter (SEQUENOM) was started and the resin-purified extension product was transferred to a 384-well SpectroCHIP (Sequenom) chip (SEQUENOM).

3.6 Mass spectrometric detection

The spotted SpectroCHIP chip is analyzed by MALDI-TOF, and the detection result is typed by TYPER 4.0 software (sequenom) and output.

Example 2 analysis of polymorphic site rs2853817 of mitochondrial DNA and susceptibility to high altitude pulmonary edema this example used the method established in example 1 to analyze the genotype of the polymorphic site rs2853817 of mitochondrial DNA of a participant.

Statement of ethics

Each participant signed an informed consent form and the study was approved by the seventh medical center of the liberty military and the medical ethics committee of the general hospital of the tibetan liberty military.

Study object

The study objects are two populations obtained by the seventh medical center of the liberty military from 2018 to 2019 of the general hospital of the tibetan liberty military, wherein the population 1 consists of 49 patients with high altitude pulmonary edema (case group) and 58 normal persons (control group); population 2 (validation sample) peripheral blood samples were taken from 33 patients with high altitude pulmonary edema (case group) and 19 normal persons (control group). In the two groups, 82 patients with high altitude pulmonary edema and 77 normal people are Han nations of Chinese male unrelated in blood margin in plain region. 82 patients with high altitude pulmonary edema aged 19-60 years, with the average (30.7 + -10.7) years old; 77 normal individuals were from a general physical examination population aged 19-55 years, with a mean (25.4 + -6.1) of years. All people had no history of smoking, drinking, and mitochondrial-related diseases such as cardiovascular disease, diabetes, etc., and had no history of altitude trips before, and were all people who arrived at the same altitude tibetan pizza (3658 m).

In addition to meeting the above requirements, patients with high altitude pulmonary edema also need to meet the diagnosis standards of high altitude pulmonary edema, namely, on-site diagnosis standards and clinical diagnosis standards.

On-site diagnostic criteria:

(1) the disease is developed. The recent arrival at the plateau (typically above 3000m altitude).

(2) Signs. Dyspnea at rest, chest tightness, oppression and feeling, cough, white or pink foamy sputum, weakness or reduced mobility.

(3) Signs. One or both lung fields show moist rales or wheezing, cyanosis medially, tachypnea, tachycardia.

At least two of the above symptoms and signs can be diagnosed.

Clinical diagnostic criteria:

(1) the sputum reaches plateau (generally above an altitude of 3000 m) recently, and dyspnea, cough and white or pink foamy sputum appear at rest.

(2) Cyanosis medialis, rales moist lung.

(3) The chest X-ray is the main basis of diagnosis, and the lung fields at one side or two sides of the lung with the lung portal as the center are in a spot-sheet shape or cloud-flocculent infiltration shadow which is often in diffuse and irregular distribution and can also be fused into a large-sheet shadow; the heart shadow is normal, but pulmonary hypertension and enlarged right heart can also be seen.

(4) Clinical examination and electrocardiogram examination can be performed to eliminate myocardial infarction, heart failure and other cardiopulmonary diseases, and pneumonia can be eliminated.

(5) After the treatment of bed rest, oxygen inhalation and the like or low-speed rotation, the symptoms are quickly improved, and the X-ray symptoms can disappear in a short time.

1. Determination of mitochondrial DNA polymorphic site rs2853817 genotype:

according to the method of example 1, genomic DNAs of peripheral blood samples of 49 patients with high altitude pulmonary edema and 58 normal persons of population 1 were extracted, respectively, and PCR amplification, single base extension reaction and genotyping were performed. The distribution of genotype frequencies of the rs2853817 polymorphic sites of the two groups of mitochondrial DNAs is shown in Table 4. In 49 patients with high altitude pulmonary edema, 10 individuals with the rs2853817 genotype C are present, and the genotype frequency is 20.4%; 39 individuals with the rs2853817 genotype of T have a genotype frequency of 79.6%. In 58 normal people, 3 individuals with the rs2853817 genotype C exist, and the genotype frequency is 5.2%; 55 individuals with the rs2853817 genotype of T have genotype frequency of 94.8%. All data were processed using an independent sample Person test with SPSS17.0(SPSS inc., USA) statistical software.

In all samples, the distribution frequency of C genotype in case group (49 patients with high pulmonary edema) was significantly higher than that in control group (p-value of 0.016 and df of 1) compared with that in control group (58 normal persons), indicating that there was a significant difference in distribution frequency of C and T genotypes between case group and control group (p < 0.05). An increase in the C genotype was found to increase the probability of HAPE after correction by Logistic regression analysis (OR 4.701; 95% CI, 1.214-18.204; p-adjust ═ 0.035). The results show that the mitochondrial DNA polymorphic site rs2853817 is obviously related to the plateau pulmonary edema. The risk of HAPE in the population carrying the C allele at the T16172C (rs2853817) site is significantly higher than in the population carrying the T allele at the T16172C (rs2853817) site.

TABLE 4 genotype frequencies of the rs2853817 polymorphic sites in mitochondrial DNA of case and control groups

Note: p-value: person' s²test, p-adjust: adjust p-value, OR: ratio of ratios, CI: a confidence interval.

2. Verification of mitochondrial DNA polymorphic site rs2853817 genotype

According to the same principle and method, 33 cases of patients with high altitude pulmonary edema and 19 cases of normal persons in the population 2 are selected again, the genome DNA of the peripheral blood sample is extracted, and the genome DNA is used as a template, and a forward primer is used: 5'-CAGCCACCATGAATATTGTACG-3' (SEQ ID NO: 4 in the sequence Listing); reverse primer: 5'-GTTAGGCTGGTGTTAGGGTTC-3' (sequence 5 in the sequence table) to carry out PCR amplification on genome DNA fragments including the rs2853817 site of the mitochondrial DNA gene and sequence, and the result shows that two PCR products are obtained together, wherein the sequences of the two PCR products are sequence 6 in the sequence table, and in the sequence 6, y is c or t. The rs2853817 locus is located at the 65 th position of the sequence 6, the nucleotide is C or T, when the nucleotide is T, the rs2853817 genotype is T, and when the nucleotide is C, the rs2853817 genotype is C. The distribution of the genotype frequencies of the rs2853817 polymorphic sites of the two groups of mitochondrial DNAs is shown in Table 5. The result shows that 11 individuals with the rs2853817 genotype of C in 33 patients with high altitude pulmonary edema have the genotype frequency of 33.3 percent; 22 individuals with the rs2853817 genotype T have genotype frequency of 66.7%. In 19 normal people, 1 individual with the rs2853817 genotype C has the genotype frequency of 5.3 percent; 18 individuals with the rs2853817 genotype of T have a genotype frequency of 94.7%. Data were processed for statistics using an independent sample Person test of SPSS17.0(SPSS inc., USA) statistical software.

TABLE 5 genotype frequencies of the rs2853817 polymorphic sites in mitochondrial DNA of case and control groups

In all the samples tested, the distribution frequency of the C genotype in the case group (33 patients with high pulmonary edema) was significantly higher than that in the control group (p-value 0.021 and df 1) compared with the control group (19 normal persons), indicating that the distribution frequency of the C, T genotype was significantly different between the case group and the control group (p < 0.05). An increase in the C genotype was found to increase the probability of HAPE after correction by Logistic regression analysis (OR 9.000; 95% CI, 1.059-76.479; p-adjust ═ 0.049). The results show that the mitochondrial DNA polymorphic site rs2853817 is obviously related to the plateau pulmonary edema. Consistent with the results in table 4.

All the results prove that the risk of HAPE occurrence of the population carrying the C allele at the T16172C (rs2853817) site is significantly higher than that of the population carrying the T allele at the T16172C (rs2853817) site, and rs2853817 can be used for screening individuals susceptible to high altitude pulmonary edema, predicting the susceptibility of people to high altitude pulmonary edema, screening individuals carrying the genes susceptible to high altitude pulmonary edema and evaluating the risk of high altitude pulmonary edema.

Sequence listing

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Claims

1. The application of the substance for detecting the polymorphism or genotype of rs2853817 in the human genome in preparing products for screening or assisting in screening susceptible individuals or non-susceptible individuals of high altitude pulmonary edema.

2. The application of the substance for detecting the polymorphism or genotype of rs2853817 in a human genome in the preparation of products for detecting or assisting in detecting the susceptibility of high altitude pulmonary edema.

3. The application of the substance for detecting the polymorphism or genotype of rs2853817 in the human genome in the preparation of products for detecting or assisting in detecting the risk of the plateau pulmonary edema.

4. The application of the substance for detecting the polymorphism or genotype of rs2853817 in the human genome in the preparation of products for evaluating or assisting in evaluating the risk of the plateau pulmonary edema.

5. Use according to any one of claims 1 to 4, characterized in that: the polymorphism or genotype of the rs2853817 is T or C, the T is the polymorphism or genotype of the site rs2853817 which is T, and the C is the polymorphism or genotype of the site rs2853817 which is C; the risk of suffering from high altitude pulmonary edema of the individual with the rs2853817 polymorphism or genotype C is higher than or is candidate to be higher than that of the individual with the rs2853817 polymorphism or genotype T.

6. The application of the substance for detecting the polymorphism or genotype of rs2853817 in a human genome in preparing products for screening or assisting in screening the susceptible genotype of the plateau pulmonary edema or the non-susceptible genotype of the plateau pulmonary edema.

7. Use according to claim 6, characterized in that: the susceptible genotype of the plateau pulmonary edema is T, and the non-susceptible genotype of the plateau pulmonary edema is C; the T is the genotype with the locus rs2853817 as T, and the C is the genotype with the locus rs2853817 as C.

8. Use according to any one of claims 1 to 7, characterized in that: the substance for detecting the polymorphism or the genotype of the rs2853817 in the human genome contains a PCR primer and/or a single-base extension primer for amplifying the DNA segment of the human genome including the rs 2853817.

9. A product containing a substance for detecting rs2853817 polymorphism or genotype in human genome, which is any one of a) to d):

10. The product of claim 9, wherein: the substance for detecting the polymorphism or the genotype of the rs2853817 in the human genome contains a PCR primer and/or a single-base extension primer for amplifying the DNA segment of the human genome including the rs 2853817.