CN108330196B - Application of rs12252 polymorphism in detection of influenza virus antibody - Google Patents
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- C—CHEMISTRY; METALLURGY
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- 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
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Abstract
The invention discloses application of rs12252 polymorphism in detection of influenza virus antibodies. The technical scheme protected by the invention is that the application of a substance for detecting rs12252 polymorphism or genotype in a human genome in preparing a product for detecting or assisting in detecting the level of an antibody against an H1N1pdm09 influenza virus in young people, the application in preparing a product for screening young people who are inoculated with a vaccine for preventing influenza caused by the H1N1pdm09 influenza virus, or the application in preparing a product for detecting the resistance of young people to the H1N1pdm09 influenza virus. The invention can be used for screening young people needing to be recommended to inject the vaccine for preventing influenza caused by the H1N1pdm09 influenza virus.
Description
Technical Field
The invention relates to application of rs12252 polymorphism in the field of biomedicine in detection of influenza virus antibodies.
Background
Single Nucleotide Polymorphism (SNP) refers to a variation of a single nucleotide in a genome, which is the most minute variation unit and is a variation form formed by substitution, inversion, insertion or deletion of a single nucleotide pair. Single nucleotide polymorphisms are a high density of genetic markers on the genome, with more than 3000 tens of thousands of SNPs found in the human genome. As a third generation genetic marker, the SNP has a large number and dense distribution, and is easy to detect, so the SNP is an ideal genotyping target.
rs12252 is the SNP site of a biallelic polymorphism on human chromosome 11p5.5, the mutation being a switch (T/C, A/G on its complementary strand), which is located in the interferon inducible transmembrane protein 3(IFITM3) gene.
The gene for interferon-induced transmembrane protein 3(IFITM3, also known as 1-8U) was originally identified in 1984 as being discovered during screening of cDNA from INF-treated neuroblastoma, which clones a cDNA library derived from human lymphocytes. IFITM3 is translationally expressed in most tissues and highly induces interferon expression. Previous studies have shown that IFITM3 belongs to the murine gene family, is shorter, contains 2 transmembrane domains of proteins (5-18kDa), has higher core sequence similarity, but has evolutionary differences in the N and C-termini. Human homologous genes (IFITM1, IFITM2, and IFITM3) all cluster within an 18-kb genomic sequence on chromosome 11 and mediate cellular developmental processes including cell adhesion, immune cell regulation, germ cell homing and maturation.
In 2009 influenza a (H1N 1/2009) outbreaks in mexico (H1N1pdm09) and rapidly spread to infect humans and swine herds in other countries around the world. The H1N1pdm09 influenza virus is derived from pigs and is a human, pig and avian recombinant virus.
Currently, vaccination is the primary method for controlling influenza. Children, old people, chronic patients and pregnant women all recommend vaccination to avoid serious diseases and complications caused by influenza infection.
Disclosure of Invention
The technical problems to be solved by the invention are how to detect the level of antibodies against the H1N1pdm09 influenza virus in young people, how to screen young people who recommend vaccination, or how to detect the resistance of young people against the H1N1pdm09 influenza virus.
In order to solve the technical problem, the invention firstly provides any one of the following applications 1-3:
1. use of a substance that detects rs12252 polymorphism or genotype in the human genome for the manufacture of a product for detecting the level of antibodies against the H1N1pdm09 influenza virus in young people;
2. the use of a substance that detects the polymorphism or genotype of rs12252 in the human genome in the preparation of a product for screening young people for suggested vaccination; the vaccine is used for preventing influenza caused by H1N1pdm09 influenza virus;
3. application of a substance for detecting rs12252 polymorphism or genotype in human genome in preparation of a product for detecting resistance of young people to H1N1pdm09 influenza virus.
rs12252 is the SNP site of a biallelic polymorphism on human chromosome 11p5.5, the variation being the transition (T/C, A/G on its complementary strand).
In the above application, the young people may be 17-23 years old. The young people may be 17-22 years old people who have not been infected with influenza virus nor vaccinated with influenza vaccine for 3 months. The young person may also be a person aged 18-23 years who was vaccinated against influenza vaccine 12-18 months ago.
In the application, the influenza vaccine can be a vaccine for preventing influenza caused by the H1N1pdm09 influenza virus. The influenza vaccine can also be a vaccine for preventing influenza caused by H1N1pdm09 influenza virus, H3N2 influenza A virus and B influenza virus.
In the above application, the influenza vaccine is an inactivated influenza virus vaccine. The active ingredients of the influenza vaccine are inactivated H3N 2A influenza virus, inactivated H1N1pdm09 influenza virus and inactivated B influenza virus.
In the above application, the rs12252 genotype is CC, CT or TT. Wherein CC is homozygote with rs12252 locus as C, TT is homozygote with rs12252 locus as T, and CT is heterozygote with rs12252 locus as T and C.
In the above use, when the young people are 17-22 years old and not infected with influenza virus nor influenza vaccine for 3 months, the antibody level against H1N1pdm09 influenza virus in the young people of CC genotype is higher than the antibody level against H1N1pdm09 influenza virus in the young people of TT genotype and the young people of CT genotype; the antibody level against the H1N1pdm09 influenza virus in the young population of the CT genotype was not statistically different from the antibody level against the H1N1pdm09 influenza virus in the young population of the TT genotype.
In the above use, when said young human is an 18-23 year old human vaccinated with influenza between 12-18 months ago, the antibody level against H1N1pdm09 influenza virus in said young human of CC genotype and said young human of CT genotype is higher than the antibody level against H1N1pdm09 influenza virus in said young human of TT genotype; the antibody level against the H1N1pdm09 influenza virus in the young population of the CC genotype was not statistically different from the antibody level against the H1N1pdm09 influenza virus in the young population of the CT genotype.
Experiments prove that in young people with the age of 17-22 years who are not infected with influenza virus and not inoculated with influenza vaccine within 3 months, the antibody level against the H1N1pdm09 influenza virus in the young people with the CC genotype is higher than the antibody level against the H1N1pdm09 influenza virus in the young people with the CT genotype and the TT genotype; the antibody level against the H1N1pdm09 influenza virus in the young population of the CT genotype was not statistically different from the antibody level against the H1N1pdm09 influenza virus in the young population of the TT genotype. (ii) in young people aged 18-23 years who were vaccinated 12-18 months ago with an influenza vaccine, the antibody level against H1N1pdm09 influenza virus in young people of the CC genotype and young people of the CT genotype is higher than the antibody level against H1N1pdm09 influenza virus in young people of the TT genotype; the antibody level against the H1N1pdm09 influenza virus in the young population of the CC genotype was not statistically different from the antibody level against the H1N1pdm09 influenza virus in the young population of the CT genotype. In young populations aged 17-22 years of age vaccinated 14-28 days ago with influenza, antibody levels against H1N1pdm09 influenza virus in young populations of the CC genotype were not statistically different from antibody levels against H1N1pdm09 influenza virus in young populations of the TT genotype and young populations of the CC genotype.
Experiments prove that in young people with the age of 17-22 years who are not infected with influenza virus and not inoculated with influenza vaccine within 3 months, the antibody titer of the CC genotype against the H1N1pdm09 influenza virus at the 14 th day and the 28 th day after the inoculation of the influenza vaccine is increased by 2 times and is far lower than the antibody titer against the H1N1pdm09 influenza virus after the inoculation of the TT genotype group (the antibody titer against the H1N1pdm09 influenza virus at the 14 th day after the inoculation is increased by 10 times and the antibody titer against the H1N1pdm09 influenza virus at the 28 th day after the inoculation is increased by 8 times); the population of CC genotype 14 days after inoculation with influenza vaccine produced an increase in antibody titer against H1N1pdm09 influenza virus of 48.6% or more in 4-fold proportion of people, much lower than the TT genotype (the population producing an increase in antibody titer against H1N1pdm09 influenza virus of 78.6% or more in 4-fold proportion of people). It is demonstrated that vaccines for the prevention of influenza caused by the H1N1pdm09 influenza virus are more effective in secreting specific antibodies against the H1N1pdm09 influenza virus to the population with the TT genotype.
In the above application, the detection of the polymorphism or genotype of rs12252 in the human genome can be specifically determined by detecting the nucleotide type of rs 12252.
In the above application, the substance for detecting the polymorphism or genotype of rs12252 in human genome may be a reagent and/or an apparatus for determining the polymorphism or genotype of rs12252 by at least one of the following methods: DNA sequencing, restriction enzyme fragment length polymorphism, single-strand conformation polymorphism, denaturing high performance liquid chromatography, SNP chip, TaqMan probe technology and Sequenom MassArray technology. Wherein, the reagents and/or instruments required for determining the polymorphism or genotype of rs12252 by using the Sequenom MassArray technology comprise PCR primer pair, extension primer based on single base extension reaction, phosphatase (such as Shrimp Alkaline Phosphatase (SAP)), resin, chip, MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight mass spectrometry) and other reagents and instruments required by the Sequenom Massarrray technology; reagents and/or instruments required for determining the polymorphism or genotype of rs12252 by using the restriction enzyme fragment length polymorphism include a PCR primer pair and a restriction endonuclease; the SNP chip includes a chip based on nucleic acid hybridization reaction, a chip based on single base extension reaction, a chip based on allele-specific primer extension reaction, a chip based on "one-step" reaction, a chip based on primer ligation reaction, a chip based on restriction enzyme reaction, a chip based on protein DNA binding reaction, and a chip based on fluorescent molecule DNA binding reaction.
In the above application, the substance for detecting rs12252 polymorphism or genotype in human genome may comprise a PCR primer pair for amplifying a genomic DNA fragment including rs12252 and/or restriction endonuclease MscI. The substance for detecting the polymorphism or genotype of rs12252 in the human genome can also be only a PCR primer pair and/or a restriction enzyme MscI for amplifying a genomic DNA fragment including rs 12252.
In one embodiment of the invention, the polymorphism and genotype of rs12252 is determined using restriction enzyme fragment length polymorphisms. The PCR primer pair has no special requirements on the sequence, as long as the PCR primer pair can amplify a genome DNA fragment including rs12252, and can be specifically single-stranded DNA shown by SEQ ID No.1 and SEQ ID No.2 in a sequence table. The restriction enzyme may specifically be MscI.
In the above application, the product for detecting the antibody level against the H1N1pdm09 influenza virus in young people, the product for screening the young people who are recommended to be vaccinated and the product for detecting the resistance of young people to the H1N1pdm09 influenza virus can be reagents, kits or systems. In such applications, the system may include reagents, kits, and/or instruments.
In the above applications, the product for detecting the antibody level against the H1N1pdm09 influenza virus in young people, the product for screening the young people who are suggested to be vaccinated and the product for detecting the resistance of young people against the H1N1pdm09 influenza virus can all comprise the substance for detecting the polymorphism or genotype of rs12252 in the human genome, and can further comprise a system for quantitatively detecting the antibody level against the H1N1pdm09 influenza virus. The system for quantitatively detecting the antibody level against the H1N1pdm09 influenza virus can be a reagent and/or an instrument required for detecting the antibody level against the H1N1pdm09 influenza virus by enzyme-linked immunosorbent assay.
Herein, the antibody level against H1N1pdm09 influenza virus may be the antibody level against H1N1pdm09 influenza virus in plasma.
In practical applications, the substance for detecting the polymorphism or genotype of rs12252 and the system for quantitatively detecting the level of antibodies against the H1N1pdm09 influenza virus can be combined to detect the level of antibodies against the H1N1pdm09 influenza virus. If the polymorphism or genotype of the rs12252 of the young person to be detected can be detected firstly, if the genotype of the young person to be detected is TT, the antibody level of the young person to be detected to the H1N1pdm09 influenza virus is predicted to be lower, the antibody level of the young person to be detected to the H1N1pdm09 influenza virus can be further quantitatively detected, the resistance of the young person to be detected to the H1N1pdm09 influenza virus is determined, and whether the young person to be detected is recommended to be injected with the vaccine for preventing influenza caused by the H1N1pdm09 influenza virus is determined.
The invention can be used for screening young people needing to be recommended to inject the vaccine for preventing influenza caused by the H1N1pdm09 influenza virus.
Drawings
FIG. 1 is an electropherogram of the restriction of PCR amplification products using MscI restriction enzyme; wherein M is a DNA molecular weight standard (50bp Ladder); samples 1-1, 1-2 and 1-3 are CT genotype enzyme digestion products; samples 2-1, 2-2 and 2-3 are CC genotype enzyme digestion products; samples 3-1, 3-2 and 3-3 are TT genotype restriction products.
FIG. 2 is the level of antibodies to influenza H1N1pdm09 (A), to influenza A H3N2 (B) and to influenza B (C) in young healthy human volunteers of CC, CT and TT genotypes prior to influenza vaccine injection. One point in fig. 2 is one case.
FIG. 3 is the levels of antibodies against the H1N1pdm09 influenza virus at different times after injection of influenza vaccine in young healthy volunteers of CC, CT and TT genotypes. Wherein, A is the antibody level against H1N1pdm09 influenza virus of three genotype groups at the 14 th day after injection of influenza vaccine, B is the antibody level against H1N1pdm09 influenza virus of three genotype groups at the 28 th day after injection of influenza vaccine, C is the antibody level against H1N1pdm09 influenza virus of three genotype groups at the 12 th month after injection of influenza vaccine, D is the antibody level against H1N1pdm09 influenza virus of three genotype groups at the 18 th month after injection of influenza vaccine, and E is the antibody level against H1N1pdm09 influenza virus of CC and TT genotype groups at the 0 th day before injection of influenza vaccine, at the 14 th day after injection of influenza vaccine, at the 28 th day, at the 12 th month and at the 18 th month. One point in A-D of FIG. 3 is a case.
FIG. 4 shows the fold increase of antibody titers against H1N1pdm09 influenza virus at day 14, day 28 and month 12 after the injection of influenza vaccine for the young human healthy volunteers of CC and TT genotypes compared to the day before the injection of influenza vaccine (day 0) (A) and the population ratio of the antibody titers against H1N1pdm09 influenza virus at day 14 after the injection of influenza vaccine for the young human healthy volunteers of CC and TT genotypes (B) of 4 or more times. One point in a of fig. 4 is one case; in B of FIG. 4, Positive is the proportion of persons who had an antibody titer against the H1N1pdm09 influenza virus increased 4-fold or more, and Negative is the proportion of persons who had an antibody titer against the H1N1pdm09 influenza virus increased 4-fold or less.
Detailed Description
The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention.
The experimental procedures in the following examples are conventional unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1, IFITM3rs12252 is a single nucleotide polymorphic site associated with antibody levels against H1N1pdm09 influenza virus in young people
rs12252 is the SNP site of a biallelic polymorphism on human chromosome 11p5.5, the mutation being the transition (T/C, A/G on its complementary strand), which is located in the IFITM3 gene. The rs12252 genotype is CC, CT or TT. Wherein CC is homozygote with rs12252 locus as C, TT is homozygote with rs12252 locus as T, and CT is heterozygote with rs12252 locus as T and C.
First, subject and sample
99 healthy young volunteers aged 17-22 years were not infected with influenza virus nor inoculated with influenza vaccine within 3 months.
Genomic DNA of each human was extracted.
Genotyping of the second and rs12252 site
(1) Amplification of nucleotide fragments containing SNP sites
Designing primers according to the flanking sequence of rs12252, wherein a forward primer F: 5'-GAAAAGGAAACTGTTGAGAACCGAA-3' (SEQ ID NO.1), reverse primer R: 5'-GAGCCTCCTCCTAAACCTGCAC-3' (SEQ ID NO.2), and amplifying the nucleotide fragment of the SNP to be detected, wherein the PCR product is SEQ ID NO.3 in the sequence table. The rs12252 site is located at 140bp of SEQ ID NO.3, where the nucleotide is C or T, and when the nucleotide is T, it can be recognized by MscI endonuclease (the recognition sequence is TGG ^ CCA).
Wherein the PCR reaction system is calculated by 50 ul: 150-one 200 ng/. mu.l human genome DNA 1. mu.l, 10. mu.M primers F and R each 2. mu.l, Premix Taq HS 25. mu.l, and ddH for the remainder2O; wherein, Premix Taq HS is a product of TaKaRa company (product number: DR 028A). Premix Taq Hot Start Version (TaKaRa Co.) was used.
The PCR reaction conditions are as follows: 10 minutes at 95 ℃; 60 seconds at 95 ℃, 30 seconds at 55 ℃, 30 seconds at 72 ℃ and 35 cycles; 5 minutes at 72 ℃.
(2) Selecting proper endonuclease according to the difference of the 142 th nucleotide for PCR-RFLP
The PCR product is cut by MscI endonuclease, and the reaction system is calculated by 20 mu l: PCR amplification product 10. mu.l, Fast digestion MscI enzyme (Fast Digest MScI, Fermentas) 1. mu.l, 10 XFastdigest Green buffer 2. mu.l, nuclease-free ddH2O17. mu.l. The reaction conditions are as follows: water bath at 37 deg.C, enzyme digestion for 30 min.
Then, the resulting enzyme-cleaved product was electrophoresed in 2% agarose gel, stained with ethidium bromide, and observed in a gel imaging system.
Preparing glue: and (3) washing a vessel contacted with the glue with distilled water, naturally airing at room temperature, pouring 2% agarose gel containing Golden View into the template, inserting the comb with 13 holes, and pulling out the comb after the glue is naturally polymerized to prepare the 2% agarose gel containing 13 holes.
Electrophoresis: to 15. mu.l of the digested product, 3. mu.l of 6 Xloading buffer was added, and the mixture was subjected to loading detection at a constant pressure of 100V and electrophoresis for 2 hours.
Determining the genotype of the locus in the detection population according to the PCR-RFLP result. When the 140bp nucleotides of the PCR product are all C, the MscI endonuclease can not identify the site, namely the PCR product can not be cut, only one band is arranged in the gel, the length is 562bp, and the genotype is marked as CC type; when the nucleotides at 140bp are all T, the PCR amplified fragment can be cut into two fragments, one fragment is 420bp, the other fragment is 142bp, and the genotype is marked as TT type; when 140bp contains both C and T, the gel electrophoresis contains three bands with lengths of about 562bp, 420bp and 142bp, and the genotype is marked as a heterozygous CT type. (FIG. 1)
The results showed that 35 of 99 healthy young volunteers were of CC genotype, 36 of CT genotype and 28 of TT genotype.
Third, comparing the age, sex, neutrophil, lymphocyte, monocyte and eosinophil level of 99 healthy young volunteers before the injection of influenza vaccine
The levels of leukocytes, neutrophils, lymphocytes, monocytes and eosinophils in the peripheral blood of 99 healthy young volunteers were examined before the injection of influenza vaccine, and the results showed that the age, sex, leukocytes, neutrophils, lymphocytes, monocytes and eosinophils levels of 99 healthy young volunteers were not significantly different among the different genotype groups (table 1).
TABLE 1 comparison of age, sex, neutrophil, lymphocyte, monocyte and basophil levels
Fourthly, comparison of antibody levels against H1N1pdm09 influenza virus in three genotypes of young people before injection of influenza vaccine
On the day of influenza vaccine injection, peripheral blood of the above 99 young healthy volunteers was taken before the injection of influenza vaccine (day 0), and the serum of the case was examined for the level of antibodies against H1N1pdm09 influenza virus, the level of antibodies against H3N2 influenza virus, and the level of antibodies against influenza B virus using hemagglutination inhibition assay (HAI). Hemagglutinin used in hemagglutination inhibition assay was A/California/7/2009 (H1N1) pdm 09-analogous strain (NYMCX-179A) venom, A/Switzerland/9715293/2013 (H3N2) -analogous strain (IVR-175) venom, B/Pregji/3073/2013 venom, respectively. The titer of the antibody was determined as the reciprocal of the highest dilution of serum in which complete inhibition occurred in the hemagglutination inhibition assay.
The results are shown in fig. 2, indicating that in young people aged 17-22 years who were not infected with influenza virus nor inoculated with influenza vaccine within 3 months, the antibody level against H1N1pdm09 influenza virus (antibody titer 91.13 ± 19.20) in the young people of CC genotype was significantly higher than the antibody level against H1N1pdm09 influenza virus (antibody titer 34.46 ± 6.55) in the young people of TT genotype, with a P value of 0.003 therebetween; the antibody level against H1N1pdm09 influenza virus in the young population of the CC genotype was significantly higher than the antibody level against H1N1pdm09 influenza virus in the young population of the CT genotype (antibody titer 48.61 ± 7.90), with a P value of 0.040 between; the antibody level against the H1N1pdm09 influenza virus in the young population with the CT genotype was not significantly different from the antibody level against the H1N1pdm09 influenza virus in the young population with the TT genotype, with a P value of 0.276 between them. In young people aged 17-22 years who were not infected with influenza virus nor vaccinated for influenza within 3 months, antibody levels against H3N2 influenza virus and antibody levels against influenza B virus were not significantly different between young people of the CC genotype, the CT genotype and the TT genotype. Demonstrating that the genotype of rs12252 was significantly correlated with H1N1pdm09 influenza virus antibody levels in young people who were not infected with either influenza virus or influenza vaccine for 3 months.
Fifth, comparison of antibody levels against H1N1pdm09 influenza virus in three genotypes of young people after different periods of time of injection of influenza vaccine
The influenza virus split vaccine used in the experiment is prepared by adopting influenza virus A1, influenza virus A3 and influenza virus B current-year epidemic strains or similar strains recommended by WHO, culturing in fertilized eggs produced by healthy chicken flocks, splitting by using TritonX-100, inactivating formaldehyde and purifying. The active ingredients are as follows: every 0.5ml of antigen containing the following strains: A/California/7/2009 (H1N1) pdm 09-analogous strain (NYMCX-179A) 15. mu.g hemagglutinin, A/Switzerland/9715293/2013 (H3N2) -analogous strain (IVR-175) 15. mu.g hemagglutinin, B/Pregji/3073/201315. mu.g hemagglutinin. Other components: a buffer comprising sodium chloride, disodium hydrogen phosphate dihydrate, potassium dihydrogen phosphate, potassium chloride and water for injection.
The 99 young healthy volunteers were injected with the split influenza virus vaccine at 0.5ml per person, and blood was collected at 14 th, 28 th, 12 th and 18 th months after injection, and the serum of the cases was examined for the level of antibodies against the H1N1pdm09 influenza virus using hemagglutination inhibition assay (HAI). The hemagglutinin used in the hemagglutination inhibition assay was A/California/7/2009 (H1N1) pdm 09-analogous strain (NYMCX-179A) virus fluid. The titer of the antibody (titer of the antibody) was determined as the reciprocal of the highest dilution of serum in which complete inhibition occurred in the hemagglutination inhibition assay.
The results are shown in fig. 3, and the antibody levels in most volunteers were elevated after vaccination with influenza split vaccine. Antibody levels against H1N1pdm09 influenza virus did not differ significantly between young populations of the CC genotype, the CT genotype and the TT genotype in young populations aged 17-22 years of age that were neither infected with influenza virus nor vaccinated within 3 months at day 14 and day 28 after vaccination with influenza vaccine (a and B in fig. 3). Demonstrating that the levels of antibodies to H1N1pdm09 influenza virus in young populations of the CC genotype at an age of 17-22 years that were vaccinated 14-28 days ago were not statistically different from the levels of antibodies to H1N1pdm09 influenza virus in young populations of the TT genotype and young populations of the CC genotype.
But at 12 months and 18 months after inoculation with influenza virus split vaccines, the differences between the different genotypes reappeared (C, D and E in fig. 3): in young people aged 18-23 years who were vaccinated 12 months ago with influenza, the level of antibodies against H1N1pdm09 influenza virus (antibody titer of 129.4 ± 16.53) in young people of the CC genotype was higher than the level of antibodies against H1N1pdm09 influenza virus (antibody titer of 73.41 ± 11.39) in young people of the TT genotype, with a P-value of 0.020 between them; the level of antibodies against the H1N1pdm09 influenza virus in young people of the CT genotype (antibody titre of 124.6 ± 14.69) was higher than the level of antibodies against the H1N1pdm09 influenza virus in young people of the TT genotype with a P value of 0.018 between them; the antibody level against the H1N1pdm09 influenza virus in the young population of the CC genotype was not significantly different from the antibody level against the H1N1pdm09 influenza virus in the young population of the CT genotype, with a P value of 0.837 between them. In young people aged 18-23 years who were 18 months ago and vaccinated with influenza, the antibody level against H1N1pdm09 in young people of the CC genotype (antibody titer 162.40 ± 24.47) was higher than the antibody level against H1N1pdm09 in young people of the TT genotype (antibody titer 93.21 ± 22.53), with a P value of 0.030 in between; the level of antibody against H1N1pdm09 influenza virus in young people with the CT genotype (antibody titer 182.50 +/-26.58) was higher than that of antibody against H1N1pdm09 influenza virus in young people with the TT genotype, with a P value of 0.017 between the two; the antibody level against the H1N1pdm09 influenza virus in the young population of the CC genotype was not significantly different from the antibody level against the H1N1pdm09 influenza virus in the young population of the CT genotype, with a P value of 0.7256 between them.
Sixth, the influenza vaccine is more effective in secreting specific antibody against H1N1pdm09 influenza virus for TT genotype people
Comparing the fold increase of antibodies against H1N1pdm09 influenza virus at different time points before (day 0) influenza vaccination for the CC and TT genotype groups in step five above. The results show that: the antibody titers against H1N1pdm09 influenza virus of CC genotype at day 14 and 28 after vaccination with influenza vaccine increased 2-fold, much less than the fold increase in secreted antibodies after vaccination with TT genotype population (10-fold increase in antibody titer against H1N1pdm09 influenza virus at day 14 after vaccination, p 0.028; 8-fold increase in antibody titer against H1N1pdm09 influenza virus at day 28 after vaccination, p 0.014; a in fig. 4). In addition, comparing the ratio of the increase of the antibody titer against H1N1pdm09 influenza virus at 14 days after the inoculation of influenza vaccine to different genotype groups of people, the results showed that: the percentage of persons with CC genotype who produced a 4-fold or greater increase in antibody titer against H1N1pdm09 influenza virus was 48.6% (17/35), much lower than the TT genotype (78.6%, 5/28, p ═ 0.015, B in fig. 4).
It is demonstrated that vaccines for the prevention of influenza caused by the H1N1pdm09 influenza virus are more effective in secreting specific antibodies against the H1N1pdm09 influenza virus to the population with the TT genotype.
Sequence listing
<110> the Beijing Youtoan Hospital affiliated to the university of capital medical science
Application of polymorphism of <120> rs12252 in detection of influenza virus antibody
<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> human (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 (1)
1. Use of a substance for detecting rs12252 polymorphism or genotype in the human genome for the manufacture of a product for assessing the titer level of specific antibodies against an H1N1pdm09 influenza virus in young adults vaccinated against a vaccine for the prevention of influenza caused by the H1N1pdm09 influenza virus;
wherein the young people are people of 17-23 years of age.
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| 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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| 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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| "IFITM3 Rs12252-C Variant Increases Potential Risk for Severe Influenza Virus Infection in Chinese Population";Yong Pan等;《Front. Cell.Infect. Microbiol》;20170630;第7卷(第294期);第1页摘要，第5页图2,结果、讨论部分 * |
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