CN105567862A - Application of CDK18 in preparing products for diagnosing coronary heart disease - Google Patents
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Abstract
The invention discloses application of a CDK18 gene as a molecular marker for diagnosing coronary heart disease. The research proves that compared with the normal person, the mRNA expression level of the CDK18 gene in the blood of a patient with coronary heart disease is obviously lowered. A kit for diagnosing coronary heart disease can be prepared according to the relevance between the CDK18 gene and coronary heart disease. The kit can be used for judging the occurrence of coronary heart disease by detecting the mRNA level of the CDK18 gene in the blood of a subject. The kit can be widely used in clinic.
Description
Technical field
The invention belongs to molecular diagnosis field, relate to a kind of molecular marker for diagnosis of coronary heart disease, be specifically related to the application of molecular marker-CDK18 gene in the product preparing diagnosis of coronary heart disease in blood.
Background technology
Atherosclerotic Cardio-Cerebrovascular Diseases has become the major health concern that world wide is paid close attention to.The World Health Organization (WHO) the report display of 2004, the annual cardiovascular disorder in the whole world takes the death toll Da Gaoda 1,720 ten thousand caused as the leading factor with coronary heart disease and cerebral apoplexy, account for 1/3rd of all death tolls.Estimate that this numeral of the year two thousand twenty will increase by 50% further, up to 2,500 ten thousand, cardiovascular disorder is global human " number one killer ".The extensive perspective study carried out in China also shows, and heart disease has become the major causes of death of Chinese population, apportion man, the 2nd and the 1st of women die reason.Myocardial infarction 500,000 people newly sends out every year in China, and the Hazard Factor of being correlated with along with living-pattern preservation and atherosclerosis continue to increase, and coronary heart disease and myocardial infarction are fallen ill yet will in lasting ascendant trend.
A large amount of research datas shows, coronary heart disease is a kind of complex disease, is caused by multiple minor gene and environmental factors interact for a long time.Therefore identify the tumor susceptibility gene relevant to coronary heart disease or Disease-causing gene, in crowd, further screening increases the tumor susceptibility gene determination susceptible individual of disease risks, will contribute to the onset risk prediction of coronary heart disease, new drug development, diagnosis and individualized treatment.
Summary of the invention
In order to make up the deficiencies in the prior art, the object of the present invention is to provide a kind of molecular marker that can be used for coronary heart disease early diagnosis.Compare the diagnostic method of traditional coronary heart disease, use gene marker to carry out diagnosis of coronary heart disease and there is promptness, specificity and susceptibility, thus make patient just can know disease risks in early days in disease, for risk height, take corresponding prevention and therapy measure.
To achieve these goals, the present invention adopts following technical scheme:
The invention provides the application of product in the instrument preparing diagnosis of coronary heart disease detecting CDK18 genetic expression.
Further, the product of the detection CDK18 genetic expression mentioned above comprises: by RT-PCR, real-time quantitative PCR, immunodetection, in situ hybridization, chip or high-flux sequence detection of platform CDK18 gene expression dose with the product of diagnosis of coronary heart disease.
Further, the product of described RT-PCR diagnosis of coronary heart disease at least comprises the primer of a pair specific amplified CDK18 gene; The product of described real-time quantitative PCR diagnosis of coronary heart disease at least comprises the primer of a pair specific amplified CDK18 gene; The product of described immunodetection diagnosis of coronary heart disease comprises: the antibody be combined with CDK18 protein-specific; The product of described in situ hybridization diagnosis of coronary heart disease comprises: with the probe of the nucleic acid array hybridizing of CDK18 gene; The product of described chip diagnosis of coronary heart disease comprises: protein chip and gene chip; Wherein, protein chip comprises the antibody be combined with CDK18 protein-specific, and gene chip comprises the probe with the nucleic acid array hybridizing of CDK18 gene.
In specific embodiment of the invention scheme, the product of described real-time quantitative PCR diagnosis of coronary heart disease at least comprises the sequence of the primer of a pair specific amplified CDK18 gene as shown in SEQIDNO.3 and SEQIDNO.4.
Preferably, described diagnostic tool comprises chip, test kit, test paper or high-flux sequence platform.Wherein, high-flux sequence platform is a kind of special diagnostic tool, and the product detecting CDK18 genetic expression can be applied to the detection of this platform realization to the expression of CDK18 gene.Along with the development of high throughput sequencing technologies, will become the structure of the gene expression profile of a people and work very easily.By contrasting the gene expression profile of Disease and normal population, easily analyze exception and the disease-related of which gene.Therefore, in high-flux sequence, the exception of the CDK18 gene purposes that also belong to CDK18 gene relevant to coronary heart disease is known, equally within protection scope of the present invention.
Present invention also offers a kind of instrument of diagnosis of coronary heart disease, described diagnostic tool comprises chip, test kit, test paper or high-flux sequence platform.
Wherein, described chip comprises gene chip, protein chip; Described gene chip comprises solid phase carrier and is fixed on the oligonucleotide probe of solid phase carrier, and described oligonucleotide probe comprises the oligonucleotide probe for CDK18 gene for detecting CDK18 gene transcription level; Described protein chip comprises solid phase carrier and is fixed on the specific antibody of CDK18 albumen of solid phase carrier; Described gene chip can be used for detecting the expression level of the multiple genes (such as, relevant to coronary heart disease multiple genes) comprising CDK18 gene.Described protein chip can be used for detecting the expression level of the multiple protein (such as relevant to coronary heart disease multiple protein) comprising CDK18 albumen.By being detected by multiple mark with coronary heart disease simultaneously, the accuracy rate of diagnosis of coronary heart disease greatly can be improved.
Wherein, described test kit comprises gene detecting kit and protein immunization detection kit; Described gene detecting kit comprises the reagent for detecting CDK18 gene transcription level; Described protein immunization detection kit comprises the specific antibody of CDK18 albumen.Further, described reagent comprises the reagent used needed in RT-PCR, real-time quantitative PCR, immunodetection, in situ hybridization or chip method detection CDK18 gene expression dose process.Preference, described reagent comprises primer for CDK18 gene and/or probe.The primer and probe that may be used for detecting CDK18 gene expression dose is easily designed according to the nucleotide sequence information of CDK18 gene.
Can be DNA, RNA, DNA-RNA mosaic, PNA or other derivative with the probe of the nucleic acid array hybridizing of CDK18 gene.The length of described probe does not limit, if complete specific hybrid, with object nucleotide sequence specific binding, any length can.The length of described probe can be as short as 25,20,15,13 or 10 bases longs.Equally, the length of described probe can grow to 60,80,100,150,300 base pairs or longer, even whole gene.Because different probe length has different impacts to hybridization efficiency, signal specificity, the length of described probe is at least 14 base pairs usually, the longlyest generally be no more than 30 base pairs, best with 15-25 base pair with the length of object nucleotide sequence complementary.Described probe self-complementary sequences most preferably less than 4 base pairs, in order to avoid affect hybridization efficiency.
Described high-flux sequence platform comprises the reagent detecting CDK18 gene expression dose.
Described test paper comprises test paper carrier and is fixed on the oligonucleotide on test paper carrier, and described oligonucleotide can detect the transcriptional level of CDK18 gene.
Further, the specific antibody of described CDK18 albumen comprises monoclonal antibody, polyclonal antibody.The specific antibody of described CDK18 albumen comprise complete antibody molecule, any fragment of antibody or modification (such as, chimeric antibody, scFv, Fab, F (ab ') 2, Fv etc.As long as described fragment can retain the binding ability with CDK18 albumen.Well known to a person skilled in the art during preparation for the antibody of protein level, and the present invention can use any method to prepare described antibody.
In specific embodiment of the invention scheme, the described primer sequence for CDK18 gene is as follows: forward primer sequence is as shown in SEQIDNO.3, and reverse primer is as shown in SEQIDNO.4.
Include but not limited to that blood, tissue juice, urine, saliva, spinal fluid etc. can obtain the body fluid of genomic dna for the CDK18 gene of diagnosis of coronary heart disease and the source of expression product thereof.In specific embodiment of the invention scheme, be blood for the CDK18 gene of diagnosis of coronary heart disease and the source of expression product thereof.
In the context of the present invention, " CDK18 gene " comprises the polynucleotide of any function equivalent of CDK18 gene and CDK18 gene.CDK18 gene comprises and has more than 70% homology with CDK18 gene (NC_000001.11) DNA sequence dna in current international common core sequence databank GeneBank, and coding identical function protein DNA sequence;
Preferably, the encoding sequence of CDK18 gene comprises any DNA molecular following:
(1) DNA sequence dna shown in SEQ ID NO.1;
(2) under strict conditions with 1) DNA sequence dna that limits hybridizes and identical function protein DNA sequence of encoding;
(3) DNA sequence dna limited with (1) or (2) has 70%, preferably, more than 90% homology, and coding identical function protein DNA molecule.
In specific embodiment of the invention scheme, the encoding sequence of described CDK18 gene is the DNA sequence dna shown in SEQIDNO.1.
In the context of the present invention, CDK18 gene expression product comprises the partial peptide of CDK18 albumen and CDK18 albumen.The partial peptide of described CDK18 albumen contains the functional domain relevant to coronary heart disease.
" CDK18 albumen " comprises any function equivalent of CDK18 albumen and CDK18 albumen.Described function equivalent comprises CDK18 albumen conservative variation's protein or its active fragments, or its reactive derivative, allelic variant, natural mutation, induced mutants, can with the protein coded by the DNA of the DNA hybridization of CDK18 under high or low stringent condition.
Preferably, CDK18 albumen is the protein with following amino acid sequences:
(1) protein be made up of the aminoacid sequence shown in SEQ ID NO.2;
(2) aminoacid sequence shown in SEQIDNO.2 had the protein derivative by the aminoacid sequence shown in SEQIDNO.2 of identical function with the aminoacid sequence shown in SEQIDNO.2 through the replacement of one or several amino-acid residue and/or disappearance and/or interpolation.The amino acid whose number replacing, lack or add is generally 1-50, preferably 1-30, and more preferably 1-20,1-10 is individual best.
(3) with the aminoacid sequence shown in SEQIDNO.2, there is at least 80% homology (being also called sequence iden), more preferably, with the aminoacid sequence shown in SEQIDNO.2 at least about 90% to 95% homology, be often 96%, 97%, 98%, 99% homology aminoacid sequence form polypeptide.
In specific embodiment of the invention scheme, described CDK18 albumen is the protein with the aminoacid sequence shown in SEQIDNO.2.
Usually, it is known that in a protein one or more amino acid whose modification can not affect the function of protein.Those skilled in the art can approve the amino acid that changes single amino acids or little per-cent or be conservative modifications to indivedual interpolations of aminoacid sequence, disappearance, insertion, replacement, and wherein the change of protein produces the protein with identity function.Intimate amino acid whose Conservative substitution tables is provided to be well known in the art.
By adding the fusion rotein that the example of the protein of an amino acid or multiple Modification of amino acid residues is CDK18 albumen.Peptide or protein with CDK18 protein fusion are not limited, as long as the fusion rotein of gained retains the biologic activity of CDK18 albumen.
CDK18 albumen of the present invention also comprises the non-conservative modification to the aminoacid sequence shown in SEQIDNO.2, as long as the protein through modifying still can retain the biologic activity of CDK18 albumen.The amino acid number suddenlyd change in this type of modifying protein normally 10 or less, such as 6 or less, such as 3 or less.
In the context of the present invention, " diagnosis of coronary heart disease " had both comprised and had judged whether experimenter has suffered from coronary heart disease, also comprised and judge whether experimenter exists the risk suffering from coronary heart disease.
Advantage of the present invention and beneficial effect:
Late Cambrian of the present invention CDK18 genetic expression is relevant to coronary heart disease, by detecting the expression of CDK18 in experimenter, can judge whether experimenter suffers from coronary heart disease or judge whether experimenter exists the risk suffering from coronary heart disease, thus instruct clinicist to provide prevention scheme or treatment plan to experimenter.
Present invention finds a kind of new molecular marked compound-CDK18 gene, compare traditional detection means, gene diagnosis more in time, more special, sensitiveer, the early diagnosis of coronary heart disease can be realized, thus reduce the mortality ratio of coronary heart disease.
Accompanying drawing explanation
Fig. 1 display utilizes QPCR to detect the differential expression of CDK18 gene in patients with coronary heart disease and normal people.
Concrete embodiment
Below in conjunction with drawings and Examples, the present invention is further detailed explanation.Following examples are only not used in for illustration of the present invention and limit the scope of the invention.The experimental technique of unreceipted actual conditions in embodiment, usual conveniently condition, the people such as such as Sambrook, molecular cloning: laboratory manual (NewYork:ColdSpringHarborLaboratoryPress, 1989) condition described in, or according to the condition that manufacturer advises.
Embodiment 1 screens the gene of differential expression in patients with coronary heart disease and normal people
1, research object:
Collect patients with coronary heart disease 5 example, normal people 5 example.
The inclusive criteria of CHD group: the Case definition of the ischemic heart disease formulated according to the World Health Organization, selects underwent coronary radiography to confirm to have the patients with coronary heart disease of one or more angiostenosis degree >=50%.The inclusion criteria of control group is: 1) when epidemiology survey, screening age, sex, nationality all match with CAD group, do not have the clinical manifestation of coronary heart disease and the examinee of Major Risk Factors through survey, physical examination, Cardiac ultrasound and Electrocardioscopy and laboratory inspection; 2) row health examination of the being in hospital coronary artery revasualization that walks abreast gets rid of coronary heart disease age, sex, national and CAD group matcher; Meet above any person to enter to elect control group as.Two groups of signature Informed Consent Forms before including research in.
Rejecting standard: the full person of CAD group-clinical data and the one simultaneously merging following disease are rejected.
(as: Congenital Heart patient, dissection of aorta, MOFE, rheumatic heart disease and there is mental disorder can not the person of cooperation).Control group: spiritedness obstacle person or check that confirmation has carotid plaques or narrow person through doppler, is rejected.
2, the extraction of total serum IgE in blood
Hundred Tyke blood rnas are used to extract the extraction that test kit carries out blood total serum IgE
(1) research object empty stomach at least 12h is required, under m seq 7:00 ~ 8:00 room temperature, venous blood samples, get whole blood 250 μ l (or 0.25g) in RNase-Free Filter column, centrifugal 2 minutes of 13000rpm, collects lower liquid, adds 0.75ml lysate RLS.
(2) homogenised sample concuss is mixed, hatch under 15-30 DEG C of condition and decompose completely to make ribosome for 5 minutes.
(3) optional step: under the condition of 4 DEG C 12,000rpm centrifugal 10 minutes, carefully gets supernatant and proceeds in a new centrifuge tube without RNA enzyme.
(4) every 1mlRLS adds 0.2ml chloroform.Cover tightly sample hose lid, it is also at room temperature hatched 3 minutes by thermal agitation 15 seconds.
(5) centrifugal 10 minutes in 4 DEG C 12,000rpm, sample can be divided into three layers: lower floor's organic phase, and the colourless aqueous phase in middle layer and upper strata, RNA is present in aqueous phase.The capacity of aqueous phase layer is approximately 60% of added RLS volume, and aqueous phase is transferred in new pipe, carries out next step operation.
(6) add 1 times of volume 70% ethanol, put upside down mixing (now may occur precipitation), the solution obtained proceeds to (adsorption column is enclosed within collection tube) in adsorption column RA together with may precipitating.
Centrifugal 45 seconds of (7) 10,000rpm, discard waste liquid, adsorption column are recovered collection tube again.
(8) add 500 μ l protein liquid removal RE, centrifugal 45 seconds of 12,000rpm, discards waste liquid.
(9) add 700 μ l rinsing liquid RW, centrifugal 60 seconds of 12,000rpm, discards waste liquid.
(10) add 500 μ l rinsing liquid RW, centrifugal 60 seconds of 12,000rpm, discards waste liquid.
(11) put back in sky collection tube by adsorption column RA, centrifugal 2 minutes of 12,000rpm, removes rinsing liquid as far as possible, in order to avoid residual ethanol suppresses downstream reaction in rinsing liquid.
(12) take out adsorption column RA, put into a centrifuge tube without RNA enzyme, add the water of 50-80 μ l without RNA enzyme according to expection RNA output in the middle part of adsorption film, room temperature places 2 minutes, centrifugal 1 minute of 12,000rpm, collects elutriant.
3, the purity check (NanoDrop1000 spectrophotometer) of RNA sample
NanoDrop1000 spectrophotometer detects RNA sample, and OD260/OD280 is 1.8-2.2.
4, the mass analysis (AgilentTechnologies2100Bioanalyzer) of RNA sample
AgilentTechnologies2100Bioanalyzer detects RNA sample quality, observation 28SrRNA and 18SrRNA master tape obviously, nothing is degraded, RNA Perfection Index is qualified, concentration meets the requirements of the requirement meeting RNA-seq order-checking cDNA library structure, may be used for library construction and order-checking.
5, high-throughput transcript profile order-checking
(1) the RNA-seq section of reading location
First the low-quality section of reading is removed and obtain the clean section of reading, then utilize TopHatv1.3.1 will clean fragment to mate with reference to genome (hg19) with UCSCH.sapiens, the index built in advance of H.sapiensUCSChg19 version is downloaded from TopHat homepage, and as reference genome, when utilizing TopHat to mate with genome, each section of reading (defaulting to 20) is allowed to have multiple coupling site, maximum 2 mispairing.TopHat sets up possible shearing site storehouse according to exon region and GT-AG shear signal, will not navigate to the genomic section of reading navigate on genome according to these shearing site storehouses.We use the system default parameter of TopHat method.
(2) transcript abundance assessment
What match reads segment file by Cufflinksv1.0.3 process, and RNA-seq segment number is carried out the relative abundance of standardized calculation transcript by Cufflinksv1.0.3.FPKM value refers in each 1,000,000 sequenced fragments the segment number matching the long exon region of specific gene 1kb.The fiducial interval of FPKM estimated value is calculated by Bayesian inference method.The GTF comment file of the reference that Cufflinks uses downloads (Homo_sapiens.GRCh37.63.gtf) from Ensembl database.
(3) detection of difference expression gene
By the EnsemblGTF file of download be transferred to Cuffdiff by the source document that TopHat mates, Cuffdiff uses original matching files again to estimate the gene expression abundance of the transcript listed in GTF file, and checkout discrepancy is expressed.In Cuffidff exports, only have q value < 0.01, test display is successfully more just considered to differential expression.
6, result
RNA-seq result shows, and compared with normal people, in patients with coronary heart disease blood, the mRNA level in-site of CDK18 gene significantly declines, and difference has statistical significance (P<0.05).
The gene of differential expression in embodiment 2QPCR experimental verification patients with coronary heart disease and normal people
1, research object:
Screening criteria with embodiment 1, patients with coronary heart disease and normal people each 50 example.
2, the extraction of total serum IgE in blood
Step is with embodiment 1.
3, reverse transcription
The synthesis of cDNA uses TaqMan Reverse Transcription box, (comprises 5.5mmol/LMgCl at 10 μ l reverse transcription buffer
2, random 6 nucleotide primers of 2.5mmol/L, 4URNA enzyme inhibitors and 31.25UMultiScribe ThermoScript II) and reverse transcription is carried out to the total serum IgE of 200ng, operate according to the following steps: 25 DEG C of 10min, 37 DEG C of 60min, 95 DEG C of 5min.
4、QPCR
Real-time fluorescence detection method is adopted to carry out quantitatively mRNA abundance.CDNA as above-mentioned acquisition increases on ABIPrism7700 sequential detector, and CDK18 gene primer, 18S ribosomal RNA gene design of primers are as follows:
CDK18：
Upstream primer: 5 '-ACATTGGCTTTGGGAAAC-3 ' (SEQIDNO.3);
Downstream primer: 5 '-CCTATGCCACAGTCTTCA-3 ' (SEQIDNO.4),
18SrRNA：
Upstream primer: 5 '-AATCAGGGTTCGATTCCGGA-3 ' (SEQIDNO.5);
Downstream primer: 5 '-CCAAGATCCAACTACGAGCT-3 ' (SEQIDNO.6),
The expression of CDK18 gene uses 18S ribosome-RNA(rRNA) to make internal reference.Carry out PCR with the 2 times amount SYBRGreenPCRmastermix (comprising upstream primer and 5 μm of ol/L downstream primers of 5 μm of ol/L) of 12.5 μ l, final volume is 25 μ l.PCR condition is: 95 DEG C of 10min, 50 circulations (95 DEG C of 30s, 56 DEG C of 30s, 72 DEG C of 30s).ABIprism7700 type Sequence Detector is used to carry out Real-Time Monitoring to the fluorescence that reporter fluorescence dyestuff is launched.Fluorescent emission amount reflection cycle number, and read by the software of Sequence Detector, provide the significant cycle number threshold value of pcr amplification, value and the genomic dna logarithm of cycle number are linear, use Δ Δ CT method to carry out relative quantification.
5, statistical method
Result data is all represent in the mode of mean+SD, adopts SPSS13.0 statistical software to carry out statistical study, and difference between the two adopts t inspection, thinks to have statistical significance as P<0.05.
6, result
As shown in Figure 1, compared with normal people, in patients with coronary heart disease blood, the mRNA level in-site of CDK18 gene significantly reduces result, and difference has statistical significance (P<0.05), and result is tested with RNA-Seq.
The explanation of above-described embodiment is just for understanding method of the present invention and core concept thereof.It should be pointed out that for the person of ordinary skill of the art, under the premise without departing from the principles of the invention, can also carry out some improvement and modification to the present invention, these improve and modify and also will fall in the protection domain of the claims in the present invention.
Claims (10)
1. detect the application of product in the instrument preparing diagnosis of coronary heart disease of CDK18 genetic expression.
2. application according to claim 1, is characterized in that, described product comprises: by RT-PCR, real-time quantitative PCR, immunodetection, in situ hybridization, chip or high-flux sequence detection of platform CDK18 gene expression dose with the product of diagnosis of coronary heart disease.
3. application according to claim 2, is characterized in that, the product of described RT-PCR diagnosis of coronary heart disease at least comprises the primer of a pair specific amplified CDK18 gene; The product of described real-time quantitative PCR diagnosis of coronary heart disease at least comprises the primer of a pair specific amplified CDK18 gene; The product of described immunodetection diagnosis of coronary heart disease comprises: the antibody be combined with CDK18 protein-specific; The product of described in situ hybridization diagnosis of coronary heart disease comprises: with the probe of the nucleic acid array hybridizing of CDK18 gene; The product of described chip diagnosis of coronary heart disease comprises: protein chip and gene chip; Wherein, protein chip comprises the antibody be combined with CDK18 protein-specific, and gene chip comprises the probe with the nucleic acid array hybridizing of CDK18 gene.
4. application according to claim 3, is characterized in that, the primer of a pair specific amplified CDK18 gene that the product of described real-time quantitative PCR diagnosis of coronary heart disease at least comprises is as shown in SEQIDNO.3 and SEQIDNO.4.
5. for an instrument for diagnosis of coronary heart disease, it is characterized in that, described instrument can carry out diagnosis of coronary heart disease by the expression detecting CDK18 gene in sample.
6. instrument according to claim 5, is characterized in that, described instrument comprises chip, test kit, test paper or high-flux sequence platform.
7. instrument according to claim 6, is characterized in that, described chip comprises gene chip, protein chip; Described gene chip comprises solid phase carrier and is fixed on the oligonucleotide probe of solid phase carrier, and described oligonucleotide probe comprises the oligonucleotide probe for CDK18 gene for detecting CDK18 gene transcription level; Described protein chip comprises solid phase carrier and is fixed on the specific antibody of CDK18 albumen of solid phase carrier; Described test kit comprises gene detecting kit and protein immunization detection kit; Described gene detecting kit comprises the reagent for detecting CDK18 gene transcription level; Described protein immunization detection kit comprises the specific antibody of CDK18 albumen; Described test paper comprises the reagent for detecting CDK18 gene transcription level; Described high-flux sequence platform comprises the reagent for detecting CDK18 gene transcription level.
8. instrument according to claim 7, is characterized in that, the reagent of described detection CDK18 gene transcription level comprises primer for CDK18 gene and/or probe.
9. instrument according to claim 8, its spy is characterised in that, the described primer sequence for CDK18 gene is as follows: forward primer sequence is as shown in SEQIDNO.3, and reverse primer is as shown in SEQIDNO.4.
10. the instrument according to any one of claim 5-9, is characterized in that, described sample is blood.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105861735A (en) * | 2016-06-17 | 2016-08-17 | 北京泱深生物信息技术有限公司 | Application of RAP1B in coronary heart disease diagnosis |
| CN106801095A (en) * | 2017-02-14 | 2017-06-06 | 徐州市中心医院 | Application of the PRRT1 genes in diagnosis of coronary heart disease product is prepared |
| CN108796069A (en) * | 2018-07-03 | 2018-11-13 | 北京泱深生物信息技术有限公司 | Diagnosis marker-ING1 the genes of myocardial infarction |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105861735A (en) * | 2016-06-17 | 2016-08-17 | 北京泱深生物信息技术有限公司 | Application of RAP1B in coronary heart disease diagnosis |
| CN106801095A (en) * | 2017-02-14 | 2017-06-06 | 徐州市中心医院 | Application of the PRRT1 genes in diagnosis of coronary heart disease product is prepared |
| CN108796069A (en) * | 2018-07-03 | 2018-11-13 | 北京泱深生物信息技术有限公司 | Diagnosis marker-ING1 the genes of myocardial infarction |
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| CN105567862B (en) | 2018-12-14 |
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