CN108330196A - Application of the polymorphism of rs12252 in detecting Antibody of Influenza - Google Patents
Application of the polymorphism of rs12252 in detecting Antibody of Influenza Download PDFInfo
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Abstract
The invention discloses application of the polymorphism of rs12252 in detecting Antibody of Influenza.The technical solution that the present invention is protected is the application in the product for the antibody level that the substance of the polymorphism or genotype of rs12252 in detection human genome is directed to H1N1pdm09 influenza viruses in preparation detection or auxiliary detection young people, the application in preparation screening suggestion inoculates against the product of the young people of the vaccine of influenza caused by H1N1pdm09 influenza viruses or is preparing detection young people to the application in the product of the resistance of H1N1pdm09 influenza viruses.The present invention can be used for screening and need to suggest the young people that injection prevents the vaccine of influenza caused by H1N1pdm09 influenza viruses.
Description
Technical field
The present invention relates to application of the polymorphism of rs12252 in biomedical sector in detecting Antibody of Influenza.
Background technology
Single nucleotide polymorphism (single nucleotide polymorphism, SNP) refers to genome single nucleotide acid
Variation, it is most small change anticoincidence unit, is to be formed by variation to displacement, transversion, insertion or missing by single nucleotide acid
Form.Single nucleotide polymorphism is highdensity genetic marker on genome, and the SNP quantity being had found in human genome is super
Cross 30,000,000.It is large number of, densely distributed as third generation genetic marker SNP, it is easy to detect, thus be ideal Genotyping
Target.
Rs12252 is the SNP site of a two equipotential polymorphisms on human chromosome 11p5.5, which is conversion (T/
C is then A/G on its complementary strand), which is located in interferon-induced transmembrane protein 3 (IFITM3) gene.
The gene of interferon-induced transmembrane protein 3 (IFITM3, also referred to as 1-8U) initially determines that in 1984, be from
INF has found that Clone Origin is in the cDNA library of human lymphocyte during treating neuroblastoma screening cDNA.IFITM3
Can in most of tissues accurate translation, and height inducing interferon is expressed.It is previous research shows that IFITM3 belongs to musculus cdna
Family, shorter, the albumen (5-18kDa) containing 2 transmembrane domains have higher core sequence similitude, but N and C-
There are evolution differences for end.The homologous gene (IFITM1, IFITM2 and IFITM3) of the mankind is gathered in one on No. 11 chromosomes
In the genome sequence of a 18-kb, and the growth course of mediated cell, including cell adherence, immunocyte are adjusted, reproduction cell
It goes back to the nest and ripe.
The influenza (H1N1pdm09) of H1N1 in 2009/2009 is broken out in Mexico, and rapidly the sprawling infection whole world its
The people of his countries and regions and swinery.H1N1pdm09 influenza viruses derive from pig, are a kind of people, pig, three source recombinant virus of fowl.
Currently, vaccine inoculation is the main method of prevention and control influenza.Children, old man, chronic, pregnant woman suggest being inoculated with
Vaccine avoids them because infection influenza leads to the generation of serious disease and complication.
Invention content
The technical problem to be solved by the present invention is to how detect the antibody that H1N1pdm09 influenza viruses are directed in young people
Level, how screening suggests the young people of vaccine inoculation or how to detect resistance of the young people to H1N1pdm09 influenza viruses.
In order to solve the above technical problems, present invention firstly provides any applications in following 1-3：
1, the substance for detecting the polymorphism or genotype of rs12252 in human genome is directed in preparing detection young people
Application in the product of the antibody level of H1N1pdm09 influenza viruses；
2, the substance for detecting the polymorphism or genotype of rs12252 in human genome is preparing screening suggestion vaccine inoculation
Application in the product of young people；The vaccine is the vaccine of influenza caused by preventing H1N1pdm09 influenza viruses；
3, the substance for detecting the polymorphism or genotype of rs12252 in human genome is preparing detection young people couple
Application in the product of the resistance of H1N1pdm09 influenza viruses.
Rs12252 is the SNP site of a two equipotential polymorphisms on human chromosome 11p5.5, which is conversion (T/
C is then A/G on its complementary strand).
In above application, the young people can be the age be 17-23 Sui people.The young people can be in 3 months both not
The people that the age that influenza virus infection is not inoculated with influenza vaccines again is 17-22 Sui.The young people can also be before 12-18 months
It is inoculated with the people that the age of influenza vaccines is 18-23 Sui.
In above application, the influenza vaccines can be the epidemic disease of influenza caused by preventing H1N1pdm09 influenza viruses
Seedling.The influenza vaccines can also be to prevent H1N1pdm09 influenza viruses, A type H3N2 influenza viruses and Type B influenza virus to cause
Influenza vaccine.
In above application, the influenza vaccines are inactivated influenza virus vaccines.The active constituent of the influenza vaccines is to go out
A type H3N2 influenza viruses, the H1N1pdm09 influenza viruses of inactivation and the Type B influenza virus of inactivation living.
In above application, the rs12252 genotype is CC, CT or TT.Wherein, CC is the homozygosis that the sites rs12252 are C
Type, TT are that the sites rs12252 are the homozygous of T, and CT is the heterozygous that the sites rs12252 are T and C.
In above application, it is not inoculated with when the youth had not only been uninfected by influenza virus in artificial 3 months but also the year of influenza vaccines
When the people that age is 17-22 Sui, the antibody level in the Young Patients of the CC genotype for H1N1pdm09 influenza viruses is higher than
The antibody water of H1N1pdm09 influenza viruses is directed in the Young Patients of the TT genotype and the Young Patients of the CT genotype
It is flat；For the blueness of the antibody level and the TT genotype of H1N1pdm09 influenza viruses in the Young Patients of the CT genotype
Antibody level in year crowd for H1N1pdm09 influenza viruses does not have significant difference.
In above application, as the young people that artificially age of inoculation influenza vaccines is 18-23 Sui before 12-18 months
When, for the anti-of H1N1pdm09 influenza viruses in the Young Patients of the Young Patients of the CC genotype and the CT genotype
Body level is higher than the antibody level for being directed to H1N1pdm09 influenza viruses in the Young Patients of the TT genotype；The CC genes
Antibody level in the Young Patients of type for H1N1pdm09 influenza viruses is directed to the Young Patients of the CT genotype
The antibody level of H1N1pdm09 influenza viruses does not have significant difference.
It is demonstrated experimentally that being not only uninfected by influenza virus in 3 months but also not being inoculated with the blueness that the age of influenza vaccines is 17-22 Sui
In year crowd, it is higher than the CT bases for the antibody level of H1N1pdm09 influenza viruses in the Young Patients of the CC genotype
Because being directed to the antibody level of H1N1pdm09 influenza viruses in the Young Patients of type and the Young Patients of the TT genotype；It is described
For in the antibody level of H1N1pdm09 influenza viruses and the Young Patients of the TT genotype in the Young Patients of CT genotype
There is no significant difference for the antibody level of H1N1pdm09 influenza viruses.The age of influenza vaccines was inoculated with before 12-18 months
In 18-23 Sui Young Patients, to be directed in the Young Patients of the Young Patients of the CC genotype and the CT genotype
The antibody level of H1N1pdm09 influenza viruses, which is higher than in the Young Patients of the TT genotype, is directed to H1N1pdm09 influenza viruses
Antibody level；For the antibody level of H1N1pdm09 influenza viruses and the CT bases in the Young Patients of the CC genotype
Because the antibody level for being directed to H1N1pdm09 influenza viruses in the Young Patients of type does not have significant difference.It was inoculated with before 14-28 days
In the young group that the age of influenza vaccines is 17-22 Sui, for H1N1pdm09 influenza diseases in the Young Patients of the CC genotype
The antibody level of poison is flowed with the Young Patients of the TT genotype and the Young Patients of the CC genotype for H1N1pdm09
The antibody level of Influenza Virus does not have significant difference.
It is demonstrated experimentally that being not only uninfected by influenza virus in 3 months but also not being inoculated with the blueness that the age of influenza vaccines is 17-22 Sui
In year crowd, antibody effect that CC genotype is directed to H1N1pdm09 influenza viruses in the 14th day and the 28th day after be inoculated with influenza vaccines
Valence increases 2 times, increases well below the antibody titer for being directed to H1N1pdm09 influenza viruses after TT genotype crowd's vaccine inoculations
Long multiple (the antibody titer 11-fold increase for being directed to H1N1pdm09 influenza viruses in the 14th day after inoculation, the 28th day after inoculation
Increase by 8 times for the antibody titer of H1N1pdm09 influenza viruses)；The 14th day CC genotype crowd generates after being inoculated with influenza vaccines
More than or equal to 4 times number ratios of antibody titer growth for H1N1pdm09 influenza viruses are 48.6%, are far below TT genotype
(it is 78.6% to generate and be directed to more than or equal to 4 times number ratios of antibody titer growth of H1N1pdm09 influenza viruses).Illustrate to prevent
The vaccine of influenza caused by H1N1pdm09 influenza viruses is to TT genotype crowds secretion for H1N1pdm09 influenza diseases
The specific antibody of poison is more effective.
In above application, the polymorphism or genotype of rs12252 can specifically pass through detection in the detection human genome
The nucleotide type of rs12252 determines.
In above application, detect human genome in rs12252 polymorphism or genotype substance can be by it is following extremely
A kind of few method determines the polymorphism or the reagent needed for genotype and/or instrument of rs12252：DNA sequencing, restriction enzyme slice
Segment length polymorphism, single-strand conformation polymorphism, denaturing high-performance chromatography, SNP chip, TaqMan probe technology and Sequenom
MassArray technologies.Wherein, it is determined needed for the polymorphism or genotype of rs12252 using Sequenom MassArray technologies
Reagent and/or instrument include PCR primer to, the extension primer based on single base extension, phosphatase (such as shrimp alkaline phosphatase
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 required reagents of Sequenom MassArray technologies and instrument；Utilize Restrictive fragment length polymorphism
Determine that the polymorphism of rs12252 or the reagent needed for genotype and/or instrument include PCR primer pair and restriction enzyme；SNP
Chip is included the chip based on nucleic acid hybridization reaction, the chip based on single base extension, is drawn based on allele-specific
The chip of object extension, the chip based on primer connection reaction, is based on restriction enzyme at the chip based on " one-step method " reaction
The chip of enzyme reaction, the chip based on protein D NA association reactions, and the chip based on fluorescent molecular DNA association reactions.
In above application, the polymorphism of rs12252 or the substance of genotype may include expanding in the detection human genome
The PCR primer of genomic DNA fragment including rs12252 is right/or restriction enzyme MscI.The detection human genome
The polymorphism of middle rs12252 or the substance of genotype also can be only genomic DNA fragment of the amplification including rs12252
PCR primer pair and/or restriction enzyme MscI.
In one embodiment of the present of invention, the polymorphism of rs12252 is determined using Restrictive fragment length polymorphism
And genotype.The PCR primer in sequence to not having particular/special requirement, as long as the gene including rs12252 can be amplified
DNA fragmentation is organized, concretely single stranded DNA shown in SEQ ID No.1 and SEQ ID No.2 in sequence table.The limitation
Property restriction endonuclease concretely MscI.
In above application, product, screening in the detection young people for the antibody level of H1N1pdm09 influenza viruses
It is recommended that the product of the young people of vaccine inoculation and detection young people can be examination to the product of the resistance of H1N1pdm09 influenza viruses
Agent, kit or system.In above application, the system may include reagent, kit and/or instrument.
In above application, product, screening in the detection young people for the antibody level of H1N1pdm09 influenza viruses
It is recommended that the product of the young people of vaccine inoculation and detection young people can wrap the product of the resistance of H1N1pdm09 influenza viruses
The polymorphism of rs12252 or the substance of genotype in the detection human genome are included, can also further comprise that quantitative detection is directed to
The system of the antibody level of H1N1pdm09 influenza viruses.Antibody level of the quantitative detection for H1N1pdm09 influenza viruses
System can be by enzyme linked immunoassay detection for H1N1pdm09 influenza viruses antibody level needed for reagent and/or
Instrument.
Herein, the antibody level for H1N1pdm09 influenza viruses can be being flowed for H1N1pdm09 in blood plasma
The antibody level of Influenza Virus.
In practical applications, the substance of the polymorphism for detecting rs12252 or genotype and quantitative detection can be directed to
System combined antibody water of the detection for H1N1pdm09 influenza viruses together of the antibody level of H1N1pdm09 influenza viruses
It is flat.The polymorphism or genotype that such as can first detect the rs12252 of young people to be measured, if the genotype of young people to be measured is TT,
It predicts that it is relatively low for the antibody level of H1N1pdm09 influenza viruses, H1N1pdm09 can be directed to by further quantitatively detecting it
The antibody level of influenza virus, then determine size of the young people to be measured to the resistance of H1N1pdm09 influenza viruses, then determine
Whether suggest that its injection prevents the vaccine of influenza caused by H1N1pdm09 influenza viruses.
The present invention can be used for screening and need to suggest the epidemic disease that injection prevents influenza caused by H1N1pdm09 influenza viruses
The young people of seedling.
Description of the drawings
Fig. 1 is the electrophoresis pattern for carrying out digestion to pcr amplification product using MscI restriction enzymes；Wherein, M:For DNA
Molecular weight standard (50bp Ladder)；Sample 1-1,1-2 and 1-3 are CT genotype digestion products；Sample 2-1,2-2 and 2-3 are
CC genotype digestion products；Sample 3-1,3-2 and 3-3 are TT genotype digestion products.
Fig. 2 is to be flowed for H1N1pdm09 in the young people healthy volunteer of CC, CT and TT genotype before injecting influenza vaccines
Influenza Virus antibody level (A) is directed to A type H3N2 Antibody of Influenza horizontal (B) and for Type B Antibody of Influenza level
(C).A point in Fig. 2 is a case.
Fig. 3 is that different time is directed to after the young people healthy volunteer of CC, CT and TT genotype injects influenza vaccines
H1N1pdm09 Antibody of Influenza is horizontal.Wherein, A is that the 14th day three kinds of genotype crowd are directed to after injecting influenza vaccines
H1N1pdm09 Antibody of Influenza is horizontal, and B be that the 28th day three kinds of genotype crowd are directed to after injection influenza vaccines
H1N1pdm09 Antibody of Influenza is horizontal, and C be that 12nd month three kinds of genotype crowd are directed to after injection influenza vaccines
H1N1pdm09 Antibody of Influenza is horizontal, and D be that 18th month three kinds of genotype crowd are directed to after injection influenza vaccines
H1N1pdm09 Antibody of Influenza is horizontal, and (the 0th day) on the day of E be injection before injecting influenza vaccines injects after influenza vaccines the
14 days, the 28th day, the 12nd month and 18th month CC and TT genotype crowds' is directed to H1N1pdm09 Antibody of Influenza water
It is flat.A point in the A-D of Fig. 3 is a case.
Fig. 4 is that the young people healthy volunteer of CC and TT genotype injects after influenza vaccines the 14th day, the 28th day and the 12nd
A month increased for H1N1pdm09 Antibody of Influenza potency compared with the injection same day (the 0th day) before injecting influenza vaccines
The young people healthy volunteer of multiple (A) and CC and TT genotype is directed to H1N1pdm09 influenzas on the 14th day after injecting influenza vaccines
Virus antibody titer increases by 4 times or more of number ratio (B).A point in the A of Fig. 4 is a case；In the B of Fig. 4,
Positive is for number ratio of the H1N1pdm09 Antibody of Influenza potency increase more than or equal to 4 times or more, Negative
To increase the number ratio less than 4 times for H1N1pdm09 Antibody of Influenza potency.
Specific implementation mode
The present invention is further described in detail With reference to embodiment, the embodiment provided is only for explaining
The bright present invention, the range being not intended to be limiting of the invention.
Experimental method in following embodiments is unless otherwise specified conventional method.
The materials, reagents and the like used in the following examples is commercially available unless otherwise specified.
Embodiment 1, IFITM3rs12252 are related for the antibody level of H1N1pdm09 influenza viruses to young people
Mononucleotide polymorphism site
Rs12252 is the SNP site of a two equipotential polymorphisms on human chromosome 11p5.5, which is conversion (T/
C is then A/G on its complementary strand), which is located in IFITM3 genes.Rs12252 genotype is CC, CT or TT.Wherein,
CC is that the sites rs12252 are the homozygous of C, and TT is that the sites rs12252 are the homozygous of T, and CT is that the sites rs12252 are T and C
Heterozygous.
One, subject and sample
Young people healthy volunteer 99, age 17-22 Sui be not only uninfected by influenza virus in 3 months but also be not inoculated with influenza
Vaccine.
Extract everyone genomic DNA.
Two, the Genotyping in the sites rs12252
(1) nucleotide fragments containing SNP site are expanded
According to the flanking sequence design primer of rs12252, forward primer F：5’-GAAAAGGAAACTGTTGAGAACCGAA-
3 ' (SEQ ID NO.1), reverse primer R：5 '-GAGCCTCCTCCTAAACCTGCAC-3 ' (SEQ ID NO.2), amplify and wait for
The nucleotide fragments where SNP are surveyed, PCR product is SEQ ID NO.3 in sequence table.The sites rs12252 are located at SEQ ID NO.3
140bp at, at this nucleotide be C or T, at this nucleotide be T when, can by MscI restriction endonucleases (identification sequence be TGG^
CCA it) identifies.
Wherein, PCR reaction systems are calculated as with 50 μ l：1 μ l, 10 μM of primers Fs and R of 150-200ng/ μ l human gene group DNAs are each
2 μ l, Premix Taq HS 25 μ l, surplus ddH2O；Wherein, Premix Taq HS are TaKaRa companies (article No.：
DR028A) product.Use Premix Taq Hot Start Version (TaKaRa companies).
PCR reaction conditions are：95 DEG C 10 minutes；95 DEG C 60 seconds, 55 DEG C 30 seconds, 72 DEG C 30 seconds, 35 cycle；72 DEG C 5 points
Clock.
(2) difference for being directed to the 142nd nucleotide selects restriction endonuclease appropriate to carry out PCR-RFLP
PCR product MscI endonuclease digestions, reaction system are calculated as with 20 μ l：10 μ l of pcr amplification product, rapid digestion
MscI enzymes (Fast Digest MScI, Fermentas companies) 1 μ l, 10 × FastDigest Green buffer solutions 2 μ l, it is seedless
The ddH of sour enzyme2O 17μl.Reaction condition is：37 DEG C of water-baths, digestion 30min.
Then, obtained digestion products are subjected to electrophoresis, ethidium bromide staining, gel imaging in 2% Ago-Gel
It is observed in system.
Glue：With distilled water by the vessel wash clean tactile with splicing, room temperature naturally dry will contain Golden View's
2% Ago-Gel pours into template, is inserted into the comb in 13 holes, after glue polymerize naturally, extracts comb, then is made and contains 13
2% Ago-Gel in a hole.
Electrophoresis：Into 15 μ l digestion products, addition 6 × sample-loading buffer, 3 μ l, sample detection, 100V constant pressures, electrophoresis 2 are small
When.
Genotype of the site in detecting group is determined according to the result of PCR-RFLP.The core at the 140bp of PCR product
When thuja acid is C, MscI restriction endonucleases not can recognize that the site, i.e. PCR product cannot be cut open, there was only a band in gel, long
Degree is 562bp, which is denoted as CC types；When nucleotide at 140bp is T, you can pcr amplified fragment is cut into two
Segment, one is 420bp, another segment is 142bp, which is denoted as TT types；Not only contain C at 140bp but also contains T
When, i.e., contain three bands in gel electrophoresis, length respectively may be about 562bp, 420bp and 142bp, which is denoted as heterozygous CT
Type.(Fig. 1)
The result shows that in 99 young people healthy volunteers, 35 people are CC genotype, and 36 people are CT genotype, and 28 people are
TT genotype.
Three, inject before influenza vaccines age of 99 young people healthy volunteers, gender, neutrophil leucocyte, lymphocyte,
Monocyte and eosinophil levels compare
Before injecting influenza vaccines, detect 99 young people's healthy volunteer's peripheral bloods in leucocyte, neutrophil leucocyte,
The level of lymphocyte, monocyte and eosinophil, the results showed that the age of 99 young people healthy volunteers, property
Not, leucocyte, neutrophil leucocyte, lymphocyte, monocyte and eosinophil levels are equal in different genotype crowd
Without significant difference (table 1).
Table 1, age, gender, neutrophil leucocyte, lymphocyte, monocyte and basophilic granulocyte level compare
Four, the antibody water of H1N1pdm09 influenza viruses is directed to before injection influenza vaccines in three kinds of genotype crowds of young people
Flat comparison
On the day of injection influenza vaccines, before injecting influenza vaccines (the 0th day), above-mentioned 99 young people health will is taken
The peripheral blood of hope person is detected in the serum of case using hemagglutination inhibition test (HAI) and is directed to H1N1pdm09 influenza viruses
Antibody level, the antibody level for H3N2 influenza viruses and the antibody level for Type B influenza virus.Hemagglutination presses down
Hemagglutinin used in system experiment is respectively California/7/2009 A/ (H1N1) pdm09- pleistons (NYMCX-179A) disease
Venom, Switzerland/9715293/2013 A/ (H3N2)-pleiston (IVR-175) virus liquid, the virus liquids of B/ Pu Ji/3073/2013.
To there is the potency reciprocal for antibody of the serum highest dilution completely inhibited in hemagglutination inhibition test.
The results are shown in Figure 2, shows not only to be uninfected by influenza virus in 3 months but also the age for not being inoculated with influenza vaccines is
In 17-22 Sui Young Patients, the antibody level of H1N1pdm09 influenza viruses is directed in the Young Patients of the CC genotype
(antibody titer is 91.13 ± 19.20), which is significantly higher than in the Young Patients of the TT genotype, is directed to H1N1pdm09 influenza viruses
Antibody level (antibody titer be 34.46 ± 6.55), P values between the two are 0.003；The Young Patients of the CC genotype
In be significantly higher than in the Young Patients of the CT genotype and be directed to for the antibody levels of H1N1pdm09 influenza viruses
The antibody level (antibody titer is 48.61 ± 7.90) of H1N1pdm09 influenza viruses, P values between the two are 0.040；It is described
For in the antibody level of H1N1pdm09 influenza viruses and the Young Patients of the TT genotype in the Young Patients of CT genotype
It is not significantly different for the antibody level of H1N1pdm09 influenza viruses, P values between the two are 0.276.In 3 months both
It is uninfected by influenza virus and is not inoculated in the Young Patients that the age of influenza vaccines is 17-22 Sui, for H3N2 influenza viruses
Antibody level and for Type B influenza virus antibody level in the Young Patients of the CC genotype, the blueness of the CT genotype
It is not significantly different between year crowd and the Young Patients of the TT genotype.Illustrate both to be uninfected by influenza virus in 3 months
It is not inoculated in the Young Patients of influenza vaccines again, genotype and the horizontal significantly pass of H1N1pdm09 Antibody of Influenza of rs12252
Connection.
Five, H1N1pdm09 influenza viruses are directed in three kinds of genotype crowds of young people after injection influenza vaccines different time
Antibody level comparison
This experiment influenza virus cracking vaccine used is A1 types, A3 types and the Type B influenza virus current year recommended using WHO
Epidemic strain or quasispecies are cultivated in the fertilized eggs that healthy chicken flock generates, are cracked with TritonX-100, formalin-inactivated, and pass through
It is made after purification.Its active constituent：Per antigens of the 0.5ml containing following strain：California/7/2009 A/ (H1N1) pdm09-
15 μ g hemagglutinin of pleiston (NYMCX-179A), 15 μ g blood of Switzerland/9715293/2013 A/ (H3N2)-pleiston (IVR-175)
Solidifying element, the μ g hemagglutinin of B/ Pu Ji/307,3/2,013 15.Other ingredients：Sodium chloride-containing, two hypophosphite monohydrate disodium hydrogens, biphosphate
The buffer solution of potassium, potassium chloride and water for injection.
Above-mentioned influenza virus cracking vaccine, everyone 0.5ml, respectively at note are injected to above-mentioned 99 young people healthy volunteers
It takes blood within the 14th day, the 28th day, the 12nd month and 18th month after penetrating, disease is detected using hemagglutination inhibition test (HAI)
The antibody level of H1N1pdm09 influenza viruses is directed in the serum of example.Hemagglutinin used in hemagglutination inhibition test is
California/7/2009 A/ (H1N1) pdm09- pleistons (NYMCX-179A) virus liquid.In hemagglutination inhibition test
To there is the potency (titre of antibody) reciprocal for antibody of the serum highest dilution completely inhibited.
The results are shown in Figure 3, is inoculated with the antibody level raising of most of volunteers after influenza virus cracking vaccine.It is being inoculated with
The 14th day and the 28th day after influenza vaccines, influenza virus not only it had been uninfected by 3 months but also the age for not being inoculated with influenza vaccines is 17-
In 22 years old young groups, for Young Patients, the CT of the antibody level in the CC genotype of H1N1pdm09 influenza viruses
It is not significantly different between the Young Patients of genotype and the Young Patients of the TT genotype (A and B in Fig. 3).Illustrate in 14-
In the young group that the age for being inoculated with influenza vaccines before 28 days is 17-22 Sui, it is directed in the Young Patients of the CC genotype
In the Young Patients of the Young Patients and the CC genotype of the antibody level of H1N1pdm09 influenza viruses and the TT genotype
There is no significant difference for the antibody level of H1N1pdm09 influenza viruses.
But 12nd month and 18 months after being inoculated with influenza virus cracking vaccine, the difference between different genotype goes out again
Existing (C, D and E in Fig. 3)：In the Young Patients that the age for being inoculated with influenza vaccines before 12 months is 18-23 Sui, the CC genes
For the antibody level of H1N1pdm09 influenza viruses (antibody titer is 129.4 ± 16.53) higher than described in the Young Patients of type
The Young Patients of TT genotype for H1N1pdm09 influenza viruses antibody level (antibody titer be 73.41 ± 11.39), two
P values between person are 0.020；It is (anti-for the antibody level of H1N1pdm09 influenza viruses in the Young Patients of the CT genotype
Body titre is 124.6 ± 14.69) higher than the antibody for being directed to H1N1pdm09 influenza viruses in the Young Patients of the TT genotype
Level, P values between the two are 0.018；The antibody of H1N1pdm09 influenza viruses is directed in the Young Patients of the CC genotype
Antibody level in the horizontal Young Patients with the CT genotype for H1N1pdm09 influenza viruses is not significantly different, and two
P values between person are 0.837.In the Young Patients that the age for being inoculated with influenza vaccines before 18 months is 18-23 Sui, the CC bases
Antibody level (antibody titer is 162.40 ± 24.47) because being directed to H1N1pdm09 influenza viruses in the Young Patients of type is higher than
In the Young Patients of the TT genotype for H1N1pdm09 influenza viruses antibody level (antibody titer be 93.21 ±
22.53), P values between the two are 0.030；For the anti-of H1N1pdm09 influenza viruses in the Young Patients of the CT genotype
Body horizontal (antibody titer is 182.50 ± 26.58), which is higher than in the Young Patients of the TT genotype, is directed to H1N1pdm09 influenzas
The antibody level of virus, P values between the two are 0.017；H1N1pdm09 influenzas are directed in the Young Patients of the CC genotype
The antibody level of virus is not shown with the Young Patients of the CT genotype for the antibody level of H1N1pdm09 influenza viruses
Difference is write, P values between the two are 0.7256.
Six, influenza vaccines are more effective for the specific antibody of H1N1pdm09 influenza viruses to TT genotype crowds secretion
Compare in above-mentioned steps five, CC is inoculated with influenza vaccines different time points and inoculation influenza vaccines with TT genotype crowds
Before (the 0th day) be directed to H1N1pdm09 influenza viruses the increased multiple of antibody.As a result it shows：CC genotype is in inoculation influenza epidemic disease
The 14th day and the 28th day antibody titer for H1N1pdm09 influenza viruses increases 2 times after seedling, well below TT genotype
The multiple that secretory antibody increases after crowd's vaccine inoculation (imitate after inoculation by the 14th day antibody for H1N1pdm09 influenza viruses
Valence 11-fold increase, p=0.028；The 28th day antibody titer for H1N1pdm09 influenza viruses increases by 8 times after inoculation, p=
0.014. A in Fig. 4).It is directed within the 14th day H1N1pdm09 influenza diseases in addition, comparing after different genotype crowd is inoculated with influenza vaccines
The antibody titer of poison, which increases, is more than or equal to 4 times of number ratios, as a result shows：CC genotype crowds generate to flow for H1N1pdm09
The antibody titer of Influenza Virus increases that be more than or equal to 4 times of number ratios be 48.6% (17/35), far below TT genotype (78.6%,
B in 5/28, p=0.015, Fig. 4).
Illustrate that the vaccine of influenza caused by preventing H1N1pdm09 influenza viruses is directed to TT genotype crowds secretion
The specific antibody of H1N1pdm09 influenza viruses is more effective.
Sequence table
<110>Beijing YouAn Hospital, Capital Medical University
<120>Application of the polymorphism of rs12252 in detecting Antibody of Influenza
<130> GNCFH180337
<160> 3
<170> PatentIn version 3.5
<210> 1
<211> 25
<212> DNA
<213>Artificial sequence (Artificial Sequence)
<400> 1
gaaaaggaaa ctgttgagaa ccgaa 25
<210> 2
<211> 22
<212> DNA
<213>Artificial sequence (Artificial Sequence)
<400> 2
gagcctcctc ctaaacctgc ac 22
<210> 3
<211> 562
<212> DNA
<213>People（Homo sapiens）
<220>
<221> misc_feature
<222> (140)..(140)
<223>Y is c or t
<400> 3
gaaaaggaaa ctgttgagaa ccgaaactac tggggaaagg gagggctcac tgagaaccat 60
cccagtaacc cgaccgccgc tggtcttcgc tggacaccat gaatcacact gtccaaacct 120
tcttctctcc tgtcaacagy ggccagcccc ccaactatga gatgctcaag gaggagcacg 180
aggtggctgt gctgggggcg ccccacaacc ctgctccccc gacgtccacc gtgatccaca 240
tccgcagcga gacctccgtg cccgaccatg tcgtctggtc cctgttcaac accctcttca 300
tgaacccctg ctgcctgggc ttcatagcat tcgcctactc cgtgaaggtg cgtatggccc 360
cagggaatgc tcagagggtg ccgctgagcc tggagctcca cctgcccaca tgctgcctgg 420
ggtggggact tgtgtgtccc tgtgactgtg agtttgtgtg cacctctgtc ccgtgtgtgc 480
ccacgtcagt ggctttgtct gtgtgatctg tgtgtgtgtg tggcttgggg aatctgccca 540
gtgcaggttt aggaggaggc tc 562
Claims (3)
1. detecting the substance of the polymorphism or genotype of rs12252 in human genome in preparing detection or auxiliary detection young people
For the application in the product of the antibody level of H1N1pdm09 influenza viruses.
2. detecting the substance of the polymorphism or genotype of rs12252 in human genome in the youth for preparing screening suggestion vaccine inoculation
Application in the product of people；The vaccine is the vaccine of influenza caused by preventing H1N1pdm09 influenza viruses.
3. the substance for detecting the polymorphism or genotype of rs12252 in human genome is preparing detection young people to H1N1pdm09
Application in the product of the resistance of influenza virus.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111944888A (en) * | 2019-05-15 | 2020-11-17 | 中山大学 | Application of IFITM3 SNP rs12252 genotype in predicting immune response intensity of testee |
| CN112239784A (en) * | 2019-07-19 | 2021-01-19 | 首都医科大学附属北京佑安医院 | Application of IFITM3 polymorphism in preparation of product for detecting level of H3N2 antibody secreted by elderly renal dialysis patients |
| CN113846154A (en) * | 2021-10-12 | 2021-12-28 | 首都医科大学附属北京佑安医院 | Application of rs12252 polymorphism in detection of novel coronavirus antibody |
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| CN106520988A (en) * | 2016-12-07 | 2017-03-22 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs76418789 to screening of leprosy patients |
| WO2017050988A1 (en) * | 2015-09-25 | 2017-03-30 | Universite Claude Bernard Lyon 1 | Biomarkers for early determination of severity of influenza related disease |
| CN107312828A (en) * | 2017-04-24 | 2017-11-03 | 首都医科大学附属北京佑安医院 | The mononucleotide polymorphism site related from different tumor growth rate liver cancer and its application |
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| WO2017050988A1 (en) * | 2015-09-25 | 2017-03-30 | Universite Claude Bernard Lyon 1 | Biomarkers for early determination of severity of influenza related disease |
| CN106520988A (en) * | 2016-12-07 | 2017-03-22 | 山东省皮肤病性病防治研究所 | Application of single nucleotide polymorphism rs76418789 to screening of leprosy patients |
| CN107312828A (en) * | 2017-04-24 | 2017-11-03 | 首都医科大学附属北京佑安医院 | The mononucleotide polymorphism site related from different tumor growth rate liver cancer and its application |
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| YONG PAN等: ""IFITM3 Rs12252-C Variant Increases Potential Risk for Severe Influenza Virus Infection in Chinese Population"", 《FRONT. CELL.INFECT. MICROBIOL》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111944888A (en) * | 2019-05-15 | 2020-11-17 | 中山大学 | Application of IFITM3 SNP rs12252 genotype in predicting immune response intensity of testee |
| CN112239784A (en) * | 2019-07-19 | 2021-01-19 | 首都医科大学附属北京佑安医院 | Application of IFITM3 polymorphism in preparation of product for detecting level of H3N2 antibody secreted by elderly renal dialysis patients |
| CN113846154A (en) * | 2021-10-12 | 2021-12-28 | 首都医科大学附属北京佑安医院 | Application of rs12252 polymorphism in detection of novel coronavirus antibody |
| CN113846154B (en) * | 2021-10-12 | 2024-02-13 | 首都医科大学附属北京佑安医院 | Application of rs12252 polymorphism in detection of novel coronavirus antibody |
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