CN106222289A - The application in examination heating companion thrombocytopenic syndromes patient of the rs1143634 polymorphism - Google Patents
The application in examination heating companion thrombocytopenic syndromes patient of the rs1143634 polymorphism Download PDFInfo
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- CN106222289A CN106222289A CN201610670776.3A CN201610670776A CN106222289A CN 106222289 A CN106222289 A CN 106222289A CN 201610670776 A CN201610670776 A CN 201610670776A CN 106222289 A CN106222289 A CN 106222289A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
Abstract
The invention discloses the application in examination heating companion thrombocytopenic syndromes patient of the rs1143634 polymorphism.The technical scheme that the present invention is protected is that in detection human genome, the polymorphism of rs1143634 or the material of genotype accompany the application in thrombocytopenic syndromes and the application in preparation detects heating companion's thrombocytopenic syndromes susceptibility product that new Bunyavirus causes in the heating that the preparation new Bunyavirus of examination causes.The product of thrombocytopenic syndromes patient is accompanied in generating heat that the material of the detection polymorphism of rs1143634 or genotype and other material (such as the single nucleotide polymorphism relevant with heating companion's thrombocytopenic syndromes that new Bunyavirus causes detecting other or the material of genotype) can be united the preparation new Bunyavirus of examination causes.
Description
Technical field
The present invention relates to rs1143634 polymorphism in biological technical field suffer from examination heating companion's thrombocytopenic syndromes
Application in person.
Background technology
Heating companion's thrombocytopenic syndromes is a kind of emerging infectious disease being found first in rural areas in our country.Cause of disease
Body is a kind of new Bunyavirus in bunyaviridae Phlebovirus.In heating companion thrombocytopenic syndromes Endemic Area
Territory, the serum IgG antibody Positive rate in healthy population is about 0.84%-6.37%.Although there being substantial amounts of population sick
Poison is infected, but the most few groups of people develop into Symptomatic disease, and the inherited genetic factors of prompting individuality is in the generation of this disease
Important function.Identify that the heating that new Bunyavirus causes accompanies the tumor susceptibility gene of thrombocytopenic syndromes to contribute to predicting new cloth
The individual risk of heating companion's thrombocytopenic syndromes that Buddhist nun's subvirus causes and group risk, and contribute to illustrating and this disease
Relevant pathogenesis.
Summary of the invention
The technical problem to be solved is how examination heating accompanies thrombocytopenic syndromes patient, further
It is the heating companion thrombocytopenic syndromes the patient how new Bunyavirus of examination causes.
For solving above-mentioned technical problem, present invention firstly provides following arbitrary purposes:
A1) in detection human genome, the polymorphism of rs1143634 or the material of genotype are little at preparation examination heating companion's blood
Plate reduces the application in syndrome patient's product；
A2) in detection human genome, the polymorphism of rs1143634 or the material of genotype are little at preparation detection heating companion's blood
Plate reduces the application in syndrome susceptibility product；
A3) in detection human genome, the polymorphism of rs1143634 or the material of genotype detect and heating companion's blood in preparation
Platelet reduces the application in the product of the relevant single nucleotide polymorphism of syndrome；
A4) in detection human genome, the polymorphism of rs1143634 or the material of genotype are identified or auxiliary qualification in preparation
Application in the product of the single nucleotide polymorphism relevant to heating companion's thrombocytopenic syndromes；
B1) in human genome, polymorphism or the genotype of rs1143634 are comprehensive in preparation examination heating companion's thrombocytopenia
Levy the application in patient product；
B2) in human genome, polymorphism or the genotype of rs1143634 are comprehensive in preparation detection heating companion's thrombocytopenia
Levy the application in susceptibility product；
B3) in detection human genome, the polymorphism of rs1143634 or the material of genotype subtract in examination heating companion's platelet
Application in few syndrome patient；
B4) in detection human genome, the polymorphism of rs1143634 or the material of genotype subtract in detection heating companion's platelet
Application in few syndrome susceptibility；
B5) in detection human genome, the polymorphism of rs1143634 or the material of genotype accompany platelet in detection with heating
Reduce the application in the single nucleotide polymorphism that syndrome is relevant；
B6) in detection human genome, the polymorphism of rs1143634 or the material of genotype are being identified or are being assisted qualification and send out
Application in the single nucleotide polymorphism that heat companion's thrombocytopenic syndromes is relevant；
B7) in human genome, polymorphism or the genotype of rs1143634 are suffered from examination heating companion's thrombocytopenic syndromes
Application in person；
B8) in human genome, polymorphism or the genotype of rs1143634 are easy at detection heating companion's thrombocytopenic syndromes
Application in perception.
Rs1143634 is the SNP site of two equipotential polymorphisms on human chromosome, this variation be conversion (C/T,
It is then G/A on its complementary strand).The genotype of described rs1143634 is CC, CT or TT.Described CC be rs1143634 site be C
Homozygous, described TT be rs1143634 site be the homozygous of T, described CT be rs1143634 site be the heterozygosis of C and T
Type.In described detection human genome, polymorphism or the genotype of rs1143634 specifically can be by detecting the nucleotide of rs1143634
Kind determines.
In such use, in described detection human genome, the polymorphism of rs1143634 or the material of genotype can be amplification
The PCR primer of the genomic DNA fragment including rs1143634 to and/or Single base extension primer.
In such use, the individuality of described C/T and T/T genotype is in heating companion thrombocytopenic syndromes PATIENT POPULATION
Ratio less than its ratio in comparison.
For solving above-mentioned technical problem, present invention also offers containing the polymorphism of rs1143634 in detection human genome
Or the product of the material of genotype.
The product of the material containing the polymorphism or genotype that detect rs1143634 in human genome provided by the present invention
Product, for a)-d) in any one product:
A) single nucleotide polymorphism relevant to the companion's thrombocytopenic syndromes that generates heat or the product of genotype are detected；
B) identify or assist the single nucleotide polymorphism or genotype that qualification is relevant to heating companion's thrombocytopenic syndromes
Product；
C) examination heating companion thrombocytopenic syndromes patient product；
D) detection heating companion thrombocytopenic syndromes susceptibility product.
In the said goods, in described detection human genome, the polymorphism of rs1143634 or the material of genotype can be amplification
The PCR primer of the genomic DNA fragment including rs1143634 and/or Single base extension primer.
For solving above-mentioned technical problem, present invention also offers following M1) or method M2):
M1) method of examination heating companion thrombocytopenic syndromes patient, including: detect in subject gene group to be measured
The genotype in rs1143634 site, if the genotype in rs1143634 site is CC genotype, described object to be measured is or candidate
For heating companion thrombocytopenic syndromes patient；If the genotype in rs1143634 site is CT genotype, described object to be measured is
Or candidate is non-heating companion thrombocytopenic syndromes patient；If the genotype in rs1143634 site is TT genotype, described in treat
Survey object is or candidate is non-heating companion thrombocytopenic syndromes patient；
M2) method of detection heating companion thrombocytopenic syndromes susceptibility, including: detect in subject gene group to be measured
The genotype in rs1143634 site, if the genotype in rs1143634 site is CC genotype, described object to be measured is susceptible or waits
Select susceptible heating companion's thrombocytopenic syndromes；If the genotype in rs1143634 site is CT genotype, described object to be measured is not
Susceptible or candidate the most susceptible heating companion's thrombocytopenic syndromes；If the genotype in rs1143634 site is TT genotype, described
Object to be measured is the most susceptible or thrombocytopenic syndromes is accompanied in the most susceptible heating of candidate.
In said method, detect the genotype in rs1143634 site in subject gene group to be measured and can use described detection
The polymorphism of rs1143634 or the material of genotype are carried out.
In the present invention, described PCR primer can be P1 and P2；Described P1 is following a1) to a4) in any one single stranded DNA:
A1) single stranded DNA shown in SEQ ID No.1 in sequence table；
A2) at a1) 5 ' ends and/or 3 ' ends add the single stranded DNAs that obtain of one or several nucleotide；
A3) and a1) or a2) single stranded DNA that limits has the single stranded DNA of the homogeneity of more than 85%；
A4) under strict conditions with a1) or a2) limit single stranded DNA hybridization single stranded DNA；
Described P2 can be following b1) to b4) in any one single stranded DNA:
B1) single stranded DNA shown in SEQ ID No.2 in sequence table；
B2) at b1) 5 ' ends and/or 3 ' ends add the single stranded DNAs that obtain of one or several nucleotide；
B3) and b1) or b2) single stranded DNA that limits has the single stranded DNA of the homogeneity of more than 85%；
B4) under strict conditions with b1) or b2) limit single stranded DNA hybridization single stranded DNA.
Described Single base extension primer can be following c1) to c4) in any one single stranded DNA:
C1) single stranded DNA shown in SEQ ID No.3 in sequence table；
C2) at c1) 5 ' ends and/or 3 ' ends add the single stranded DNAs that obtain of one or several nucleotide；
C3) and c1) or c2) single stranded DNA that limits has the single stranded DNA of the homogeneity of more than 85%；
C4) under strict conditions with c1) or c2) limit single stranded DNA hybridization single stranded DNA.
A2) described at a1) 5 ' ends and/or 3 ' ends add single stranded DNAs that one or several nucleotide obtain at SEQ
5 ' ends and/or the 3 ' ends of the single stranded DNA shown in ID No.1 add the single stranded DNA that one to ten nucleotide obtains.B2) described
B1) single stranded DNA that 5 ' ends and/or 3 ' hold one or several nucleotide of interpolation to obtain is at the strand shown in SEQ ID No.2
5 ' ends and/or the 3 ' ends of DNA add the single stranded DNA that one to ten nucleotide obtains.C2) described at c1) 5 ' ends and/or 3 ' ends
Adding the single stranded DNA that one or several nucleotide obtains is at 5 ' ends of the single stranded DNA shown in SEQ ID No.3 and/or 3 ' ends
Add the single stranded DNA that one to ten nucleotide obtains.
Term used herein " homogeneity " refers to the sequence similarity with native sequence nucleic acid." homogeneity " includes and this
Nucleotide sequence shown in bright SEQ ID No.1, SEQ ID No.2 or SEQ ID No.3 has 85% or higher, or 90%
Or higher, or the nucleotide sequence of 95% or higher homogeneity.Homogeneity can with the naked eye or computer software is evaluated.Make
With computer software, the homogeneity between two or more sequences can use percentage ratio (%) to represent, it can be used to evaluate phase
Close the homogeneity between sequence.
Described stringent condition is at 2 × SSC, in the solution of 0.1%SDS, hybridizes and washes film 2 times, every time at 68 DEG C
5min, again in 0.5 × SSC, in the solution of 0.1%SDS, hybridizes at 68 DEG C and washes film 2 times, each 15min；Or, 0.1 ×
SSPE (or 0.1 × SSC), 0.1%SDS solution in, hybridize under the conditions of 65 DEG C and wash film.
Above-mentioned more than 85% homogeneity, can be the homogeneity of 85%, 90% or more than 95%.
In the present invention, described heating companion's thrombocytopenic syndromes can be heating companion's platelet that new Bunyavirus causes
Reduce syndrome.Heating companion's thrombocytopenic syndromes that described new Bunyavirus causes can be that Chinese population Xin Buniya is sick
Heating companion's thrombocytopenic syndromes that poison causes.
It is demonstrated experimentally that in the heating companion thrombocytopenic syndromes PATIENT POPULATION that the new Bunyavirus of Chinese causes,
The T equipotential of rs1143634 ratio in case group is less than its ratio in matched group, has significant difference, explanation
The T equipotential of rs1143634 is the protection etc. of the heating companion thrombocytopenic syndromes patient that the new Bunyavirus of Chinese causes
Position；The C equipotential of rs1143634 ratio in case group is higher than its ratio in matched group, has significant difference, explanation
The C equipotential of rs1143634 is the risk etc. of the heating companion thrombocytopenic syndromes patient that the new Bunyavirus of Chinese causes
Position.In the heating companion thrombocytopenic syndromes PATIENT POPULATION that the new Bunyavirus of Chinese causes, rs1143634 site
In three genotype, the individuality of C/T and T/T genotype ratio in case group is less than its ratio in matched group, C/C base
Because the individuality of the type ratio in case group is higher than its ratio in matched group.With the individuality carrying C/C genotype genotype
Comparing, the individual heating companion's thrombocytopenic syndromes risk carrying C/T and T/T genotype reduces, odds ratio (Odds
Ratio, OR) it is 0.47, P=0.023, illustrate that what the new Bunyavirus of rs1143634 pleomorphism site and Chinese caused sends out
The generation of heat companion's thrombocytopenic syndromes significantly associates.
In actual applications, the polymorphism of rs1143634 or the material of genotype will can be detected with other material (such as detection
Heating companion's relevant single nucleotide polymorphism of thrombocytopenic syndromes that other Bunyavirus new to Chinese causes or
The material of genotype) it is united heating companion's thrombocytopenic syndromes that the preparation new Bunyavirus of examination Chinese causes
The product of patient.
Wherein, in detection human genome, the polymorphism of rs1143634 or the material of genotype can be by following at least one
Kind of method determines the reagent needed for the polymorphism of rs1143634 or genotype and/or instrument: DNA sequencing, restriction fragment
Length polymorphism, single strand conformation polymorphism, denaturing high-performance chromatography, SNP chip, TaqMan probe technology and Sequenom
MassArray technology.Wherein, Sequenom MassArray technology is utilized to determine polymorphism or the genotype institute of rs1143634
The reagent needed and/or instrument include PCR primer to, extension primer based on single base extension, phosphatase be (such as shrimp alkalescence phosphorus
Acid enzyme (shrimp alkaline phosphatase, SAP)), resin, chip, MALDI-TOF (matrix-assisted
Laser desorption/ionization time of fligh, matrix solid-dispersion flight time mass spectrum)
And other reagent required for Sequenom MassArray technology and instrument；TaqMan probe technology is utilized to determine
Reagent needed for the polymorphism of rs1143634 or genotype and/or instrument include that TaqMan probe, PCR primer are to, quantitative PCR
Instrument and carry out required for the software (such as 7500System SDS software) of gene type and TaqMan probe technology its
His reagent；SNP chip include chip based on nucleic acid hybridization reaction, chip based on single base extension, based on equipotential base
The chip because of the chip of specific primer extension, reacted based on " one-step method ", chip based on primer coupled reaction, based on
The chip of restriction enzyme reaction, chip based on protein D NA association reaction, and based on fluorescence molecule DNA association reaction
Chip.
Described product can be reagent or test kit, can be also the system being made up of with instrument reagent or test kit, as by drawing
Thing and the system of DNA sequencer composition, the system being made up of PCR reagent and DNA sequencing reagent and DNA sequencer, by TaqMan
Other examinations required for software that probe, PCR primer to, quantitative PCR apparatus and carry out gene type and TaqMan probe technology
Agent composition system, by PCR primer to, Single base extension primer, chip, PCR instrument and carry out gene type software and
Other reagent required for Sequenom MassArray technology and the system of instrument composition.
In one embodiment of the present of invention, Sequenom MassArray technology is used to determine the polymorphism of rs1143634
And genotype.Described PCR primer is to not having particular/special requirement in sequence, as long as the base including rs1143634 can be amplified
Because of group DNA fragmentation, the concretely single stranded DNA shown in SEQ ID No.1 and SEQ ID No.2 in sequence table.Described list
Base extends the single stranded DNA shown in SEQ ID No.3 in primer concretely sequence table.Sequenom MassArray technology institute
Other instruments needed are MassARRAY Nanodispenser RS1000 point sample instrument (SEQUENOM company).Sequenom
Chip required for MassArray technology is SpectroCHIP (Sequenom) chip.The described software tool carrying out gene type
Body is MALDI-TOF and TYPER 4.0 software (sequenom).
At a sample from Chinese population, (430 heating that new Bunyavirus causes companion's platelet subtract the present invention
Few syndrome patient and 633 new Bunyavirus inapparent infection persons) in find that rs1143634 is and Chinese Xin Buniya is sick
The single nucleotide polymorphism that heating companion's thrombocytopenic syndromes that poison causes is correlated with.Can be by the polymorphism of detection rs1143634
Or the material of genotype and other material are (as many in detected other the mononucleotide relevant with heating companion's thrombocytopenic syndromes
State property or the material of genotype) it is united the product of heating companion thrombocytopenic syndromes patient in preparation examination Chinese population
Product.
Detailed description of the invention
Being further described in detail the present invention below in conjunction with detailed description of the invention, the embodiment be given is only for explaining
The bright present invention rather than in order to limit the scope of the present invention.
Experimental technique in following embodiment, if no special instructions, is conventional method.
Material used in following embodiment, reagent etc., if no special instructions, the most commercially obtain.
Embodiment 1 detects the foundation of IL-1 β gene rs1143634 loci gene type method
1, the extraction of genomic DNA
Extract testing sample genomic DNA, carry out genotype detection with it for template.
2, the design of primer and synthesis
Use Sequenom company Genotyping Tools and MassARRAY Assay Design software design to be measured
The pcr amplification primer thing of SNP site and Single base extension primer, and transfer to biotech firm to synthesize.Detection G-CSF gene
The sequence of the specific primer pair of rs1143634 genotype is: forward primer (its entitled P1) 5 '-
ACGTTGGATGATCGTACAGGTGCATCGTG-3 ' (the SEQ ID No.1 in sequence table)；Reverse primer (its entitled P2)
5 '-ACGTTGGATGGTGCTCCACATTTCAGAACC-3 ' (the SEQ ID No.2 in sequence table).Anti-for single base amplification
The extension primer sequence answered is 5 '-CACATTTCAGAACCTATCTTCTT-3 ' (the SEQ ID No.3 in sequence table).
3, the foundation of IL-1 β gene rs1143634 loci gene type method is detected
3.1PCR expands: PCR amplification is carried out in 384 orifice plates, and each reaction system cumulative volume is 5 μ L, prepares by table 1
PCR reaction system.
The component of table 1 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/ μ L) | 0.1 |
| Ultra-pure water | 1.9 |
| DNA shown in SEQ ID No.1 | 1 |
| DNA shown in SEQ ID No.2 | 1 |
| Cumulative volume | 4 |
PCR response procedures is: 94 DEG C 4 minutes；94 DEG C 20 seconds, 56 DEG C 30 seconds, 72 DEG C 1 minute, 45 circulations；72 DEG C 3 points
Clock；4 DEG C of holdings.
3.2PCR product alkaline phosphatase treatment: after PCR reaction terminates, by PCR primer SAP (shrimp
Alkaline phosphatase, shrimp alkaline phosphotase) process, with remove system middle reaches from dNTPs, prepare SAP by table 2 anti-
Answer system.
Table 2SAP reaction system
Reaction condition is: 37 DEG C 40 minutes；85 DEG C 5 minutes；4 DEG C of maintenances.
3.3 Single base extensions: utilize 10 × single base extension buffer, single alkali after alkaline phosphatase treatment terminates
The extension primer of the single base amplification reaction shown in base extension enzyme (1.7U/ μ l) and SEQ ID No.3 carries out single base and prolongs
Stretch reaction.
Reaction condition is:
I.94 DEG C 30 seconds
II.94 DEG C 5 seconds
III.52 DEG C 5 seconds
IV.80 DEG C 5 seconds
V. III, 4 circulations are returned to
VI. II, 39 circulations are returned to
VII.72 DEG C 3 minutes
VII.4℃
3.4 resin purifications: Clean Resin resin is tiled in the resin plate of 6mg；Add 16 μ l water to extension products
In corresponding aperture；Being poured into by dried resin in extension products plate, sealer, slow speed vertical rotates 30 minutes, makes resin and reaction
Thing is fully contacted；Being centrifuged makes resin sink to bottom hole.
3.5 chip point samples: start MassARRAY Nanodispenser RS1000 point sample instrument (SEQUENOM company), will
Extension products after resin purification moves on 384 hole SpectroCHIP (Sequenom) chips (SEQUENOM company).
3.6 Mass Spectrometer Method: using MALDI-TOF to analyze the SpectroCHIP chip after point sample, testing result uses
TYPER 4.0 software (sequenom) typing also exports result.
Heating companion's platelet that embodiment 2IL-1 β gene rs1143634 site Bunyavirus new with Chinese causes subtracts
The analysis of few syndrome susceptibility
The method set up by embodiment 1, to Chinese population, (heating companion's blood that the 430 new Bunyavirus of example cause is little
Plate reduce syndrome patient and 633 examples comparison) IL-1 β gene rs1143634 loci gene type analyzed.
1, object of study
Case group: the heating companion thrombocytopenic syndromes patient that the 430 new Bunyavirus of example cause, and all meet new cloth
The heating that Buddhist nun's subvirus causes is accompanied thrombocytopenic syndromes patient clinical diagnostic criteria and examines through new Bunyavirus nucleic acid
Survey and confirm.
Matched group: 633 example Virus monitory new Bunyavirus IgM antibody is negative but new Bunyavirus IgG antibody is positive
New Bunyavirus inapparent infection person.
All object of study are the Chinese han population of consanguinity-less relation.All object of study all endorsed informed consent
Book, collects population statistics and the medical history of individual by structurized questionnaire.This research obtains the human relations of hospital of PLA 154
The approval of reason committee.
2, the determination of IL-1 β gene rs1143634 loci gene type
In crowd, the genotype in IL-1 β gene rs1143634 site and the frequency distribution of equipotential are as shown in table 3.
Result shows, in all of object of study, in case group, the frequency of C equipotential is 98.5%, and the frequency of T equipotential is
1.5%；In matched group, the frequency of C equipotential is 96.9%%, and the frequency of T equipotential is 3.1%.T equipotential frequency in case group
Lower than the frequency in matched group, there is significant difference, show that the T equipotential in rs1143634 site is Chinese Xin Buniya
The protection equipotential of heating companion's thrombocytopenic syndromes that virus causes；And the ratio that the C equipotential of rs1143634 is in case group
Higher than its ratio in matched group, there is significant difference, illustrate that C equipotential is the heating that the new Bunyavirus of Chinese causes
The risk equipotential of companion's thrombocytopenic syndromes.
In three genotype in all of object of study rs1143634 site, the individuality of C/C genotype is in case group
Ratio higher than its ratio in matched group, the individuality of C/T and T/T ratio in case group is respectively lower than corresponding gene type
Individuality ratio in matched group.In all of object of study, compared with the individuality carrying C/C genotype, carry C/T and
Heating companion's thrombocytopenic syndromes onset risk that the individual new Bunyavirus of T/T genotype causes reduces, and OR value is
0.47 [95% confidence interval (95%CI)=(0.24-0.92)；P=0.023].
Result shows, it is possible to use heating companion's blood that the new Bunyavirus of rs1143634 site examination Chinese causes is little
Plate reduces syndrome patient.
Heating companion's thrombocytopenia that table 3IL-1 β gene rs1143634 site Bunyavirus new with Chinese causes is combined
The association analysis of simulator sickness
Note: OR, odds ratio (odds ratio)；CI, confidence interval (confidence interval).
aData are through logistic regression analysis, and carried out the correction of age, sex and underlying diseases.
bχ2Inspection.
Claims (10)
1. in detection human genome, the polymorphism of rs1143634 or the material of genotype accompany thrombocytopenia in preparation examination heating
Application in syndrome patient's product.
2. in detection human genome, the polymorphism of rs1143634 or the material of genotype accompany thrombocytopenia in preparation detection heating
Application in syndrome susceptibility product.
3. in detection human genome, the polymorphism of rs1143634 or the material of genotype subtract with heating companion's platelet in preparation detection
Application in the product of the single nucleotide polymorphism that few syndrome is relevant.
4. in detection human genome, the polymorphism of rs1143634 or the material of genotype are identified in preparation or assist qualification and heating
Application in the product of the single nucleotide polymorphism that companion's thrombocytopenic syndromes is relevant.
The most following arbitrary application:
B1) in human genome, polymorphism or the genotype of rs1143634 are suffered from preparation examination heating companion's thrombocytopenic syndromes
Application in person's product；
B2) in human genome, polymorphism or the genotype of rs1143634 are easy at preparation detection heating companion's thrombocytopenic syndromes
Application in Perceptual product；
B3) in detection human genome, the polymorphism of rs1143634 or the material of genotype are combined in examination heating companion's thrombocytopenia
Application in simulator sickness patient；
B4) in detection human genome, the polymorphism of rs1143634 or the material of genotype are combined in detection heating companion's thrombocytopenia
Application in simulator sickness susceptibility；
B5) in detection human genome, the polymorphism of rs1143634 or the material of genotype accompany thrombocytopenia in detection with heating
Application in the single nucleotide polymorphism that syndrome is relevant；
B6) in detection human genome, the polymorphism of rs1143634 or the material of genotype are being identified or are being assisted qualification and heating companion
Application in the single nucleotide polymorphism that thrombocytopenic syndromes is relevant；
B7) in human genome, polymorphism or the genotype of rs1143634 are accompanied in thrombocytopenic syndromes patient in examination heating
Application；
B8) in human genome, polymorphism or the genotype of rs1143634 accompany thrombocytopenic syndromes susceptibility in detection heating
In application.
6. contain the product of the material of the polymorphism of rs1143634 or genotype in detection human genome, for a)-d) in arbitrary
Kind product:
A) single nucleotide polymorphism relevant to the companion's thrombocytopenic syndromes that generates heat or the product of genotype are detected；
B) identify or assist the single nucleotide polymorphism or the product of genotype that qualification is relevant to heating companion's thrombocytopenic syndromes
Product；
C) examination heating companion thrombocytopenic syndromes patient product；
D) detection heating companion thrombocytopenic syndromes susceptibility product.
Product the most according to claim 6, it is characterised in that: the polymorphism of rs1143634 in described detection human genome
Or the material of genotype is PCR primer and/or the Single base extension expanding the genomic DNA fragment including rs1143634
Primer.
Product the most according to claim 7, it is characterised in that: described PCR primer is P1 and P2；Described P1 is following a1)
To a4) in any one single stranded DNA:
A1) single stranded DNA shown in SEQ ID No.1 in sequence table；
A2) at a1) 5 ' ends and/or 3 ' ends add the single stranded DNAs that obtain of one or several nucleotide；
A3) and a1) or a2) single stranded DNA that limits has the single stranded DNA of the homogeneity of more than 85%；
A4) under strict conditions with a1) or a2) limit single stranded DNA hybridization single stranded DNA；
Described P2 is following b1) to b4) in any one single stranded DNA:
B1) single stranded DNA shown in SEQ ID No.2 in sequence table；
B2) at b1) 5 ' ends and/or 3 ' ends add the single stranded DNAs that obtain of one or several nucleotide；
B3) and b1) or b2) single stranded DNA that limits has the single stranded DNA of the homogeneity of more than 85%；
B4) under strict conditions with b1) or b2) limit single stranded DNA hybridization single stranded DNA.
9. according to the product described in claim 7 or 8, it is characterised in that: described Single base extension primer is following c1) to c4)
In any one single stranded DNA:
C1) single stranded DNA shown in SEQ ID No.3 in sequence table；
C2) at c1) 5 ' ends and/or 3 ' ends add the single stranded DNAs that obtain of one or several nucleotide；
C3) and c1) or c2) single stranded DNA that limits has the single stranded DNA of the homogeneity of more than 85%；
C4) under strict conditions with c1) or c2) limit single stranded DNA hybridization single stranded DNA.
The most following M1) or method M2):
M1) method of examination heating companion thrombocytopenic syndromes patient, including: detect in subject gene group to be measured
The genotype in rs1143634 site, if the genotype in rs1143634 site is CC genotype, described object to be measured is or candidate
For heating companion thrombocytopenic syndromes patient；If the genotype in rs1143634 site is CT genotype, described object to be measured is
Or candidate is non-heating companion thrombocytopenic syndromes patient；If the genotype in rs1143634 site is TT genotype, described in treat
Survey object is or candidate is non-heating companion thrombocytopenic syndromes patient；
M2) method of detection heating companion thrombocytopenic syndromes susceptibility, including: detect in subject gene group to be measured
The genotype in rs1143634 site, if the genotype in rs1143634 site is CC genotype, described object to be measured is susceptible or waits
Select susceptible heating companion's thrombocytopenic syndromes；If the genotype in rs1143634 site is CT genotype, described object to be measured is not
Susceptible or candidate the most susceptible heating companion's thrombocytopenic syndromes；If the genotype in rs1143634 site is TT genotype, described
Object to be measured is the most susceptible or thrombocytopenic syndromes is accompanied in the most susceptible heating of candidate.
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