CN111334567B - Methylation detection primer of HIF-1 alpha gene promoter region, detection method and application - Google Patents
Methylation detection primer of HIF-1 alpha gene promoter region, detection method and application Download PDFInfo
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Abstract
The invention provides a methylation detection primer of HIF-1 alpha gene promoter region, a detection method and application, which is characterized in that the invention comprises a pair of methylation specific amplification primers of the HIF-1 alpha gene promoter region, and has the advantages that the invention can conveniently and quickly realize the prediction of coronary heart disease combined with depression emotion on the molecular level, and has strong pertinence, and meanwhile, a medicament taking the methylation of the HIF-1 alpha (hypoxia inducible factor-1 alpha) gene promoter region as a target spot is expected to become a new means for intervening coronary heart disease combined with depression emotion.
Description
Technical Field
The invention relates to the field of genetic engineering, in particular to a methylation detection primer of a HIF-1 alpha gene promoter region, a detection method and application.
Background
Coronary heart disease in China increases gradually at an average speed of 5% every year, and the morbidity and mortality of coronary heart disease also increase year by year, and become the leading cause of death. The occurrence of coronary heart disease, except common biological factors, the influence of depression mood on the morbidity and prognosis of coronary heart disease is more and more obvious, and by 2020, depression will become the second factor of death and disability all over the world, second only to coronary heart disease. Currently, there is no clinical method for assessing and predicting the appearance of depressed mood in patients with coronary heart disease. Therefore, the establishment of the technical method for predicting the depressed mood of the patient has great significance for the diagnosis and treatment of the coronary heart disease.
The morbidity and mortality of coronary heart disease also rise year by year, and the disease is increased by about 5 percent of the average speed every year in China and becomes the leading cause of death; according to the statistics of the cardiovascular disease center in China, the annual expenditure for cardiovascular diseases reaches over 1300 billions, and the cardiovascular diseases become a great public health problem. The occurrence of coronary heart disease, except common biological factors, the depressed mood is closely related to the coronary heart disease, and is one of important independent risk factors of the occurrence, development and prognosis of the coronary heart disease, and by 2020, depression will become the second factor of death and disability caused all over the world, second only to the coronary heart disease. In particular, about 20% of patients admitted to acute cardiovascular events suffer depression prior to onset. In patients with acute coronary syndrome, depression can increase the death risk by 3 times, and the size of the death risk is positively correlated with the severity of depression, and patients with severe depression who suffer from coronary heart disease have extremely high death risk. The prevalence rate of the time point of suffering depression of the coronary heart disease people is 3-4 times that of the common people. About 60% of patients after acute myocardial infarction experience depression, with 15% to 22% of patients presenting with major depression. 42% of patients with early coronary heart disease combined with mild depression develop major depression after one year. Under the condition of hypoxia, the expression level of HIF-1 alpha in the myocardial cells of a patient with coronary heart disease is increased, the expression and activity of HIF-1 alpha in the myocardial cells are increased, and the glucose uptake rate of the myocardial cells can be reduced, so that the insulin resistance state of the myocardial cells is generated. Increased peripheral insulin resistance causes alterations in central nervous system insulin resistance, inducing mitochondrial and dopamine dysfunction, leading to the development of anxiety and depressive behavior. Thus, elevated peripheral HIF-1 α levels can increase the incidence of major depression.
The depressed mood of coronary heart disease is a complex disease caused by the combined action of genetic factors and environmental factors, and the epigenetic modification can provide a direct explanation for the interaction mechanism of the environmental factors and the genome. DNA methylation is most commonly an epigenetic modification, with promoter region methylation inhibiting gene transcription, manifested as a decrease in peripheral protein levels. DNA methylation regulates gene expression, causing atherosclerosis leading to the development of coronary heart disease. The depression related genes also have DNA methylation differences. Compared with a control group, the gene expression of most brain regions of depression patients is down-regulated, and high DNA methylation exists in a gene promoter region.
At present, a method for quickly, safely and easily evaluating and predicting the depressed mood of a coronary heart disease patient is lacking clinically.
Disclosure of Invention
The invention provides a methylation detection primer of a HIF-1 alpha gene promoter region, a detection method and application, which solve the problems in the prior art.
The technical scheme of the invention is realized as follows: a methylation detection primer of a HIF-1 alpha gene promoter region comprises an upstream primer SEQ ID NO.1 and a downstream primer SEQ ID NO.2 for the PCR amplification of the HIF-1 alpha gene promoter.
A methylation detection method of a HIF-1 alpha gene promoter region comprises the following steps: step 1, collecting venous blood of a patient with coronary heart disease and depression, and extracting genome DNA; step 2, processing the DNA sample by bisulfite, and centrifuging for standby at low speed for a short time; step 3, using the DNA in the step 2 as a template, and using SEQ ID NO.1 and SEQ ID NO.2 as primers to amplify the HIF-1 alpha gene promoter to obtain a PCR amplification product; step 4, agarose gel electrophoresis is carried out to detect the successfully amplified sample; step 5, performing SAP reaction on the successfully amplified sample; step 6, carrying out T-cut/RNase A digestion reaction; step 7, purifying resin; step 8, spotting the chip; and 9, calculating the methylation degree of the DNA sample by using MALDI-TOF analysis on the spotted chip.
Further, in the step 1, venous blood of a patient with coronary heart disease and depression and venous blood after drug treatment are collected, genome DNA is respectively extracted, and at least two samples are extracted from each venous blood.
Further, the PCR reaction components used in step 3 also include double distilled water, 10 XPCR buffer, deoxynucleosides, PCR amplification enzymes.
Furthermore, the content of each component in the PCR reaction components is 5.3 μ L of double distilled water, 1 μ L of 10 XPCR buffer solution, 2 μ L of deoxynucleoside, 0.25 μ L of 5U/μ L PCR amplification enzyme, 0.25 μ L of 10pmol/μ L upstream primer and 1 μ L of 10pmol/μ L downstream primer 0.2 μ L, DNA template; the PCR reaction program comprises A-95 deg.C treatment for 4min, B-95 deg.C treatment for 25sec, C-55 deg.C treatment for 40sec, D-72 deg.C treatment for 1min, E-72 deg.C treatment for 3min, F-4 deg.C treatment for not less than 30min, wherein B, C, D cycles for 40 times.
Further, the reaction components of SAP in step 5 are double distilled water for removing RNA enzyme, SAP enzyme and PCR product.
Furthermore, the reaction components of the SAP comprise 0.3 microliter of the RNase-removed double distilled water 2.2 microliter L, SAP enzyme and 4.5 microliter of the PCR product, and the SAP reaction program comprises the steps of treating at 37 ℃ for 20min, treating at 85 ℃ for 10min and treating at 4 ℃ for not less than 30 min.
Further, the reaction components of the T-cut/RNase A digestion reaction in step 6 were RNase-free double distilled water, 5 XT 7 polymerase buffer, T lysis mix, dithiothreitol, T7 RNA & DNA polymerase, ribonuclease and PCR/SAP mixture.
Furthermore, the reaction components of the T cut/RNase A digestion reaction contained 3.18. mu.L of double distilled water for RNase removal, 0.91. mu. L, T of 5 XT 7 polymerase buffer solution, 0.24. mu.L of the cleavage mixture, 0.2. mu. L, T7 RNA & DNA polymerase, 0.41. mu.L of 100mM dithiothreitol, 0.06. mu.L of ribonuclease, and 2.00. mu.L of the PCR/SAP mixture.
A kit for detecting the methylation of HIF-1 alpha gene promoter region in the depression of coronary heart disease is disclosed.
The invention has the beneficial effects that: the invention discloses a methylation detection primer of HIF-1 alpha gene promoter region, a detection method and application, which is characterized in that the invention comprises a pair of methylation specific amplification primers of the HIF-1 alpha gene promoter region, and has the advantages that the invention can conveniently and quickly realize the prediction of coronary heart disease combined with depression emotion on the molecular level, and has strong pertinence, and meanwhile, a medicament taking the methylation of the HIF-1 alpha (hypoxia inducible factor-1 alpha) gene promoter region as a target spot is expected to become a new means for intervening coronary heart disease combined with depression emotion.
The invention utilizes the characteristics and advantages that MALDI-TOF of MassARRAY has high sensitivity, high accuracy and high resolution, and does not need any fluorescent label, each reaction covers a target sequence with a plurality of CpG sites as long as 100-700bp, the standard deviation of quantitative information quantitative data of methylation degree of single CpGunit or CpG site is 0.05, and the methylation level as low as 5 percent can be detected. Avoids a plurality of defects in a plurality of previous methylation analyses: insensitive to methylation, can quantify methylation of only a few known CpG sites, and can only obtain the methylation condition of a special enzyme cutting site.
Conventional assessment of depressed mood requires assessment using multiple scales; the major and the credibility of the scale are not completely consistent, but the coronary heart disease patients are in an emergency state when being admitted, and the self-evaluation or the evaluation of the depression scale is difficult to finish physiologically. The invention is used for predicting the depressed mood of the coronary heart disease. The method realizes the prediction of the depressed emotion of the coronary heart disease patient by a novel methylation detection method, thereby realizing reasonable screening of markers while comprehensively and comprehensively inspecting the depressed emotion related markers of the coronary heart disease patient. The method provides favorable technical support for the early prediction and prognosis of the depressed mood of the coronary heart disease patient population.
The PCR amplification primer of the HIF-1 alpha gene promoter has strong specificity, avoids GC area, and has the characteristics of high sensitivity, rapid amplification, high amplification efficiency and less non-specific product.
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In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
FIG. 1 is a diagram of gel electrophoresis of a DNA sample according to the present invention after PCR amplification;
FIG. 2 is a flow chart illustrating the application of the method for detecting the methylation of the promoter region of the HIF-1 alpha gene of the invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The sample preparation and collection comprises screening coronary heart disease depression meeting the grouping condition for grouping, and the selection criteria (all criteria are met): 1. patients diagnosed with atherosclerotic coronary heart disease and with PCI according to WHO coronary heart disease diagnostic criteria (with typical angina symptoms and excluding aortic valve lesions, or a definite history of old myocardial infarction, or a definite history of acute myocardial infarction, coronary angiography finding no less than 50% coronary stenosis); 2. the diagnosis standard of DSM-IV depression is met by consultation of psychocardiologists, and the Hamilton depression scale item 17 (HAMD-17) is not less than 17 points; 3. the age is more than or equal to 35 years old. Exclusion criteria (if the subject fails to meet any of them): 1. severe neuropsychiatric disorders (alzheimer's disease, schizophrenia, bipolar disorder, etc.); 2. depression prior to coronary heart disease; 3. cachexia or severe malnutrition and severe renal function disorders (nephrotic syndrome, acute or chronic renal failure, etc.); 4. history of allergies to the medication of interest; patients with prolonged QT interval, congenital heart disease or congenital QT syndrome; 6. malignant tumors (lung cancer, stomach cancer, liver cancer, pancreatic cancer); 7. non-selective irreversible monoamine oxidase inhibitors, linezolid and pimozide are being administered.
Base line (within 5 days before escitalopram tablet treatment): for patients with coronary heart disease and depression and the general data recorded (excerpts from medical records in hospitalizations), the extent of depression was measured using the Hamilton Depression Scale 17 (HAMD-17). Collecting venous blood, performing electrocardiographic examination, and measuring vital sign indexes such as blood pressure.
Measuring the extent of depression using the HAMD-17 tool at 28 ± 5 days (second) after escitalopram tablet treatment. Collecting venous blood, performing electrocardiographic examination, and measuring vital sign indexes such as blood pressure.
And fourthly, representing the degree of the tested depression according to the value of HAMD-17, centrifuging the blood sample of the patient, extracting DNA, and storing the extracted DNA in a refrigerator of 80 ℃ below zero. After bisulfite treatment, real-time fluorescent quantitative PCR amplification was used to determine the degree of methylation modification of the HIF-1. alpha. gene. Primers used for PCR amplification are designed by using EpiDesigner software and are artificially synthesized; an upstream primer and a downstream primer.
Step one, low-permeability salting-out method for extracting genome DNA
Step two, NaHSO3Treating a DNA sample to be tested
Step three, methylation detection step of Agena MassArray system
1. PCR amplification reaction
1) Subjecting the sample to NaHSO3After treatment, the unmethylated C in the sample DNA was all converted to U (corresponding to T in the DNA) and centrifuged briefly at low speed for further use.
2) PCR reaction solutions were prepared as shown in Table 1 (reaction system preparation was performed on ice to prevent inactivation by prolonged exposure to high temperature).
TABLE 1 methylation detection of amplification PCR reaction components for the Agena MassArray System
3) Amplification PCR reaction procedure:
4) and (3) mixing 3. mu.l of PCR product with 1. mu.l of 6 loading buffer, detecting by using 1.5% agarose gel electrophoresis, observing the result after 160V and 20min, and continuing the subsequent experiment if the result is good.
5) Referring to FIG. 1, the sample electrophoretogram is used to distinguish whether PCR amplification is successful or not, for example: c03 and C05 have no amplification failure, C01, D01, C02, D02, C03, D03, C04, D04, C05, D05, C06 and D06 are post-treatment samples, and C07, D07, C08, D08, C09, D09, C10, D10, C11, D11, C12 and D12 are pre-treatment samples.
2. SAP reaction
1) The SAP reaction system is as follows (table 2):
TABLE 2 methylation detection of SAP reaction components by MassArray System
| Reagent | Final volume per reagent |
| Double distilled water for removing RNA enzyme | 2.20μL |
| SAP enzymes | 0.30μL |
| PCR product | 4.50μL |
| Total volume: | 7.00μL |
2) mu.l of SAP reaction solution was added to each well of 384-well plate, the 384-well plate was carefully covered and each well was firmly pressed to prevent evaporation during PCR procedure, and the following reaction procedure was performed after centrifugation.
3) SAP reaction procedure:
| 37℃ | 20min |
| 85℃ | 10min |
| 4℃ | not less than 30min |
3.T cutting/RNase A digestion reaction, and cutting RNA fragments into small fragments carrying CpG sites by utilizing the characteristic that RNase A can specifically recognize and cut U3' end in RNA.
1) The T-cut/RNase A digestion reaction system was as follows (Table 3):
TABLE 3T-cut/RNase A digestion reaction components
2) T cutting/RNase A digestion reaction condition: incubate at 37 ℃ for 3 h.
4. Resin purification
1) The resin was uniformly filled in an 384/6MG Dimple plate and left to dry for 10 minutes.
2) To each well of 384 sample plates was added 16. mu.l of water.
3) The 384 sample plate was gently snapped onto the sample plate, flipped over and tapped to drop the resin into each well of the sample plate.
4) And sealing the 384 sample plate by using a sealing film, and then placing the plate in a turnover plate centrifuge to rotate and mix uniformly for 30 minutes at room temperature.
5. Chip spotting: the MassARRAY nanodispenseRS 1000 sample applicator is started, and the product after resin purification is transferred to 384-well
In bioarray.
6. Massarray analysis and data output. In the same fragment, there is only a 16Da molecular weight difference between CpG and CpA, i.e., the difference between the two peaks in the mass spectrum. The spotted SpectroCHIP chip was analyzed by MALDI-TOF. Detection result is EpitYPERTMSoftware obtains raw data and a circular diagram and checks the integrity and accuracy of the data file. Storing the result in corresponding storage medium and submitting the result to biological information room for analysis.
Processing data, performing statistics and analysis, and performing pairing t test on HAMD scores and HIF-1 alpha gene methylation degrees before and after treatment of the coronary heart disease depression group; correlation and regression analysis of HIF-1 alpha gene methylation levels and HAMD score changes; independent sample t-tests were performed for differences in HAMD scores and degrees of methylation of the HIF-1. alpha. gene between the two groups.
And sixthly, calculating the methylation degree and the non-methylation degree of the sample to be detected according to the comparison of areas of a G-containing peak and an A-containing peak of MALDI-TOF analysis based on the original data, wherein the methylation degree and the non-methylation degree belong to the relative quantitative ratio of the two. The methylation degree of CpG10 and CpG21 of the C11 and C12 samples at the 180bp and 248bp is 0.40 and 0.39; the methylation degree of CpG10 and CpG21 at 180bp and 248bp of D02 and D04 is 0.68 and 0.67. After the medicine is taken, the methylation degree is increased, the expression level of HIF-1 alpha in myocardial cells is reduced, and the expression and the activity of the HIF-1 alpha in the myocardial cells are reduced. The uptake rate of glucose by cardiomyocytes was increased.
Evaluation the hamilton depression scale scores were 23.672 ± 6.410 and 9.172 ± 5.022 before admission and after 4 weeks of dosing, respectively, with reduced depression. Through the influence of the 4-week-pentahydroxytryptamine reuptake inhibitor on the scores of the hamilton depression scale after the intervention, the difference of the scores of the hamilton depression scale before and after the intervention is found to have statistical significance (p is less than 0.001).
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
SEQUENCE LISTING
<110> second subsidiary hospital of Xinjiang medical university
Methylation detection primer of HIF-1 alpha gene promoter region, detection method and application
<130>20200201
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<170>PatentIn version 3.3
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<212>DNA
<213> Artificial Synthesis
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aggaagagag tttttttgtt ttggttttat tttgg 35
<210>2
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<212>DNA
<213> Artificial Synthesis
<400>2
cagtaatacg actcactata gggagaaggc taacttcata ccccaaaaca tttactta 58
Claims (2)
1.A methylation detection primer for detecting depressed mood of coronary heart disease is characterized in that: the methylation detection primers are an upstream primer SEQ ID NO.1 and a downstream primer SEQ ID NO. 2.
2. The methylation detection primer of claim 1, used for preparing a kit for detecting depressed mood of coronary heart disease.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105567815A (en) * | 2016-01-06 | 2016-05-11 | 博淼生物科技（北京）有限公司 | Kit utilizing INS gene promoter region DNA methylation state to detect special diabetes |
| CN108424968A (en) * | 2018-06-01 | 2018-08-21 | 深圳市太科健康科技有限公司 | The DNA methylation marker of colorectal cancer and the method and kit for utilizing its detection colorectal cancer |
| CN108841928A (en) * | 2018-06-11 | 2018-11-20 | 河北医科大学 | A kind of homo mitochondrion gene group methylation detection kit and its application |
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|---|---|---|---|---|
| WO2017122917A1 (en) * | 2016-01-11 | 2017-07-20 | 서울대학교산학협력단 | Method for screening angiogenesis inhibitor targeting methylation of hif-1α |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105567815A (en) * | 2016-01-06 | 2016-05-11 | 博淼生物科技（北京）有限公司 | Kit utilizing INS gene promoter region DNA methylation state to detect special diabetes |
| CN108424968A (en) * | 2018-06-01 | 2018-08-21 | 深圳市太科健康科技有限公司 | The DNA methylation marker of colorectal cancer and the method and kit for utilizing its detection colorectal cancer |
| CN108841928A (en) * | 2018-06-11 | 2018-11-20 | 河北医科大学 | A kind of homo mitochondrion gene group methylation detection kit and its application |
Non-Patent Citations (4)
| Title |
|---|
| c-Myc、mTOR、HIF-1α基因启动子区域DNA甲基化与类风湿关节炎的相关性;黄海燕等;《中华临床免疫和变态反应杂志》;20181231;第12卷(第6期);第611-616页 * |
| GenBank登录号：NG_029606.1;NCBI;《NCBI GenBank》;20190824;第1-59859位 * |
| MALDI-TOF-MS技术在检测基因异常甲基化中的应用;刘东等;《世界最新医学信息文摘》;20181231;第18卷(第98期);第223-224、226页 * |
| mTOR、HIF-1α基因甲基化修饰与类风湿关节炎发病风险评估;黄海燕;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20190615(第06期);第E065-66页 * |
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