CN101886129A - Method for detecting mononucleotide polymorphism locus rs388915 of hypertension susceptibility genes AGTR 1 and detection kit - Google Patents
Method for detecting mononucleotide polymorphism locus rs388915 of hypertension susceptibility genes AGTR 1 and detection kit Download PDFInfo
- Publication number
- CN101886129A CN101886129A CN 201010217545 CN201010217545A CN101886129A CN 101886129 A CN101886129 A CN 101886129A CN 201010217545 CN201010217545 CN 201010217545 CN 201010217545 A CN201010217545 A CN 201010217545A CN 101886129 A CN101886129 A CN 101886129A
- Authority
- CN
- China
- Prior art keywords
- seq
- hypertension
- agtr1
- gene
- locus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention belongs to the fields of molecular biology and medicine and relates to a method for detecting hypertension susceptibility genes and a detection kit thereof. The method for detecting the essential hypertension susceptibility genes comprises the step of detecting the gene type of the locus rs388915 of angiotensin II-1 type receptor genes (AGTR1). People having rs388915 of the G gene type are more susceptible to the hypertension than the common crowd. The invention also discloses a relevant detection kit containing primers for amplifying the locus rs388915 and primers for amplifying a zone containing the locus rs388915 in the intron No.2 of the AGTR1 genes. The method is easy to operate, can be used for quickly and effectively detecting the gene type of the locus rs388915 and has low cost, thereby being a simple new method for diagnosing and treating the hypertension.
Description
Technical field
The present invention relates to molecular biology and medical field.More specifically, relate to human angiotensin II-1 receptor gene (AGTR1) (single nucleotide polymorphism, SNP) locus rs 388915 and with the detection of essential hypertension dependency.The invention still further relates to the method and the test kit that detect this SNP site.
Background technology
(essential hypertension EH) is a kind of multifactor, multigenic disease to essential hypertension, by the common morbific common and multiple cardiovascular disorder of environment and heredity factor, human health has been caused great influence.Along with the development of molecular medicine, kind surplus the hypertension relative gene that has been found that has at present had 150, but the pathogenesis of EH still imperfectly understands, and hypertensive early diagnosis and proactive problem still fail to solve fully.EH is the coefficient result of gene and environment, the variation 30%-60% attribution heredity of blood pressure.Because environmental factors can be controlled and confirm, is changeless and hypertension genetic is learned factor.Therefore, control to variable factor, as prevention, can delay and prevent hypertensive morbidity to a certain extent, but the understanding deficiency of changeless inherited genetic factors is but being had a strong impact on to a certain extent to hypertension incidence, diagnosis and treatment the hypertension Hazard Factor.Therefore the research that hypertension genetic is learned very necessary (Wang Zuoguang, Wen Shaojun, Wu Zhaosu. hypertension, tumor susceptibility gene and single nucleotide polymorphism [J]. the hypertension magazine, 2001,9:259-264).
Nearly more than two decades comes, and about the research of hypertension therapeutic concentrates on more to the control of blood pressure with to the protection of target organ, and has obtained the development of advancing by leaps and bounds.But, these means are controlling blood pressure fundamentally, at present also seldom to the research of human endogenous hypertension gene, therefore, research endogenous hypertension mechanism is one of main direction of hypertension prevention and control research from now on, has important researching value and application prospect, if by regulating endogenous hypertension mechanism treatment essential hypertension, will promote the development of China's biologic medical technology, and be the huge medical expense of the annual saving of China.
Human angiotensin II-1 receptor is renin-angiotensin-aldosterone system (Renin-angiotensin-aldosterone system, RASS) important component part, participate in regulating vasoconstriction, water sodium balance, participate in all respects of controlling of blood pressure and adjusting.After the 1 receptor combination of blood in human body in angiotensin II and Angiotensin II, can activate a series of signal transduction pathway, finally cause physiological responses such as vasoconstriction, inflammation and cell proliferation.Therefore, the single nucleotide polymorphism of the human angiotensin II-1 receptor gene (AGTR1) of coding Angiotensin II-1 receptor changes, may be closely related with human EH.AGTR1 is positioned at 3q21-25, and the about 60kb of full length gene mainly is distributed in plasma membrane, and the performance receptor active participates in the transduction of G protein signal, improves a series of biological effects of generation such as concentration of cytoplasm calcium ion with the InsP3 coupling.It all has expression in many organs of people, as: heart, skeletal muscle, brain, lung, liver and suprarenal gland etc. are one of of paramount importance acceptor in cardiovascular systems.(Zhang Jing, Zhao Wei, Yang Ze. the progress [J] of Angiotensin II-1 receptor gene and blood vessel correlated metabolism diseases relation. Chinese cardiovascular magazine, 2007,12:311-313.).Though studies show that (Shaoyong Sua at present, Jianhong Chen, Jiangong Zhao, et al.Angiotensin II type I receptor gene andmyocardial infarction:tagging SNPs and haplotype based association study.TheBeijing atherosclerosis study.Pharmacogenetics, 2004,14:673-681.), participate in by the rs388915 site, uniting the haplotype of forming in a plurality of AGTR1 site may be relevant with the morbidity of human myocardium's infarct, but does not still have the rs388915 site report relevant with EH.Because EH is the important cause of disease and the Hazard Factor (Ye Rengao of the multiple heart, cerebrovascular disease, the Lu Zaiying chief editor, " internal medicine " 2006 the 6th edition, the People's Health Publisher. the 3rd piece of chapter 6), and the research by single locus rs 388915 and human EH onset relation, the haplotype of its participation of possible explanation and the real cause of disease that comprises other cardiovascular disease incidences of myocardial infarction.
In sum, for the final treatment hypertension that realizes, this area presses for seeks the essential hypertension tumor susceptibility gene, and method, the test kit of exploitation detection essential hypertension tumor susceptibility gene, and relevant medicine.
Summary of the invention
The method and the detection kit that the purpose of this invention is to provide a kind of detection (comprising early diagnosis) hypertension susceptible gene.
The invention provides a kind of detection method of hypertension susceptibility gene, promptly detect the genotype in AGTR1 gene rs388915 site, the individual hypertensive onset risk that rs388915 has G genotype (especially GG genotype) is significantly higher than the general population.
Described rs388915, the intron 2 (fragment contig contig:NT_005612.16 position 54942902A/G) that is arranged in Mfn2 wherein, thymus nucleic acid (DNA) sequence numbering: the rs388915 position is based on SEQ IDNO:1/6; Primer 1 is based on SEQ ID NO:2/6; Primer 2 is based on SEQ ID NO:3/6; Probe 1 is based on SEQID NO:4/6; Probe 2 is based on SEQ ID NO:5/6; Amplified production is based on SEQ ID NO:6/6.
Particularly, the method comprising the steps of: (a) genomic dna of extracting sample, and amplification obtains AGTR1 gene intron 2; (b) genotype of mononucleotide polymorphism locus rs 388915 in detection step (a) product.
The primer sequence of described amplification AGTR1 gene intron 2 is shown in SEQ ID NO 2 and SEQ ID N0 3.
The genotypic probe sequence of described detection rs388915 is shown in SEQ ID NO 4 and SEQ ID NO 5.
Technology such as the order-checking that relates in the aforesaid method, amplification, extracting genomic dna all can adopt the routine operation method of this area.
The invention provides a kind of test kit that detects hypertension susceptible gene, it contains and locus rs 388915 bonded probe.
In one embodiment of the invention, with the sequence of locus rs 388915 bonded probe shown in SEQ ID NO:4 and SEQ ID NO:5.
The mentioned reagent box can also comprise the primer that comprises the zone in rs388915 site in the specific amplification AGTR1 gene intron 2.
Comprise the sequence of primer in zone in rs388915 site shown in SEQ ID NO:2 and SEQ ID NO:3 in one embodiment of the invention, with in the specific amplification AGTR1 gene intron 2.
The present invention is through research for many years, proved that first AGTR1 gene mononucleotide polymorphism locus rs 388915 (is arranged in AGTR1 intron 2, fragment contig contig:NT_005612.16 position 54942902A/G) closely related with hypertension, and found its new function: AGTR1 gene mononucleotide polymorphism locus rs 388915 is positioned at AGTR1, (fragment contig contig:NT_005612.16 position 54942902A/G) genotypic change will cause hypertensive onset risk to raise in the intron 2, wherein the association study result shows, have significant difference (p＜0.05) in the distribution of AGTR1 gene rs388915A → G in case and control group, this SNP polymorphism can change the transcription factor binding site point.Finished the present invention on this basis.
The invention provides a kind of method that the hypertension susceptibility of individuality is diagnosed, it comprises step: detect the genotype in this individual AGTR1 gene rs388915 site, judge that with this this individuality suffers from hypertensive onset risk and whether be higher than the general population.
In a preference, described difference is the single nucleotide polymorphism that is selected from rs388915.Rs388915 is positioned at Mfn2, in the intron 2 (fragment contig contig:NT_005612.16 position 54942902A/G).Wherein, thymus nucleic acid (DNA) sequence numbering: the rs388915 position is based on SEQ ID NO:1/6.
The invention provides the method whether a kind of test sample exists the single nucleotide polymorphism of AGTR1 gene, comprise step:
(a) with the genomic dna of AGTR1 gene intron 2 primer amplified samples, obtain amplified production; With
(b) genotype of mononucleotide polymorphism locus rs 388915 in the detection amplified production.
The detailed sequence in AGTR1 gene rs388915 site can be referring to network address
Http:// www.ncbi.nlm.nih.gov/Middle accession number is the nucleotide sequence of rs388915, also can be referring to SEQ ID NO 1.
The present invention checks order to (fragment contig contig:NT_005612.16 position 54942902A/G) zone in the intron in the AGTR1 gene 2.
The polymorphism in AGTR1 gene rs388915 site can be applicable to hypertensive personalized treatment.When using the polymorphism in AGTR1 gene rs388915 of the present invention site, also can use the hypertensive medicament of other treatment simultaneously.
The present invention also provides a kind of pharmaceutical composition, and it contains AGTR1 albumen and pharmaceutically acceptable carrier or vehicle safely and effectively.This class carrier comprises (but being not limited to): salt solution, damping fluid, glucose, water, glycerine, ethanol and combination thereof.Pharmaceutical preparation should be complementary with administering mode.Pharmaceutical composition of the present invention can be made into the injection form, for example is prepared by ordinary method with the physiological saline or the aqueous solution that contains glucose and other assistant agents.Pharmaceutical composition such as tablet and capsule can be prepared by ordinary method.Pharmaceutical composition such as injection, solution, tablet and capsule are made under aseptic condition.The dosage of activeconstituents is the treatment significant quantity, for example every day 0.1 microgram/kg body weight-Yue 10 mg/kg body weight.In addition, polypeptide of the present invention also can use with the other treatment agent.
When making pharmaceutical composition, be that the AGTR1 of safe and effective amount or its antagonist, agonist are applied to general Mammals, wherein this safe and effective dosage is usually at least about 0.1 microgram/kg body weight, and in most of the cases be no more than about 10 mg/kg body weight, preferably this dosage is about 0.1 microgram/kg body weight-Yue 100 mg/kg body weight.Certainly, concrete dosage also should be considered factors such as route of administration, patient health situation, and these all are within the skilled practitioners skill.
The genotype that detects the rs388915 of AGTR1 gene also can be used for auxiliary diagnosis hypertension.Detection can be at genomic dna, also can be at the amplified fragments of AGTR1 gene.The gene type assay of the rs388915 of AGTR1 gene can detect sudden change with existing technology such as Southern blotting, dna sequence analysis, PCR and in situ hybridization, or the like.
The invention provides a kind of method that detects the essential hypertension susceptible gene, it comprises the genotype in the rs388915 site of detecting human angiotensin II-1 receptor gene (AGTR1), rs388915 has the genotypic individuality of G, and hypertensive susceptibility is significantly higher than the general population.The invention also discloses the relevant detection test kit, this test kit contains the primer in amplification rs388915 site, can also comprise the primer in No. 2 intron zone of amplification AGTR1 gene.Utilize the present invention to detect the genotype in rs388915 site, method is simple, and is rapidly and efficiently with low cost, for hypertensive diagnosis and treatment provide a simple and direct new way.
Description of drawings
Fig. 1 is the detected result signal of a sample genomic dna quality.
Fig. 2 is the sequencing result sectional drawing.The genotypic sequencing result of a kind of SNP that has shown rs388915.Rs388915 is arranged in the intron 2 (fragment contig contig:NT_005612.16 position 54942902A/G) of AGTR1.
Embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to people such as normal condition such as Sambrook, molecular cloning; Condition described in the laboratory manual (New York:Cold Spring HarborLaboratory Press, 1989), or the condition of advising according to manufacturer.
Embodiment 1 fluorescent PCR detects
One, experiment material
The 7900HT quantitative real time PCR Instrument is available from American AB I company, and pcr reaction solution (TaqMan EXPressMaster Mix) is synthetic by u.s.a. applied biosystem company (ABI) customization.
Two, primer and probe design and synthetic:
Partial sequence with AGTR1 gene intron 2 is a template, uses Primer ExpressTM 2.0 software analysis TaqMan primer and probe site, and synthetic by u.s.a. applied biosystem company (ABI) customization.
Detect and use primer:
AGTR1 gene rs388915 upstream primer sequence: 5 '-TTTCTTCCACTTCTAGCACCA-3 ' (SEQ ID NO 2)
AGTR1 gene rs388915 downstream primer sequence: 5 '-ATGGATCTGGAGGTGCTATGAG-3 ' (SEQ ID NO 3)
Fluorescent probe:
AGTR1 gene rs388915 fluorescent probe 1:5 '-VIC-AATTTGCTCGCAGGGAAA-TAMRA-3 ' (SEQ ID NO4)
AGTR1 gene rs388915 fluorescent probe 2:5 '-FAM-AATTTGCTCACAGGGAAA-TAMRA-3 ' (SEQ ID NO5)
Three, pattern detection:
Experiment detects 910 routine hypertension cases and 496 routine normal control crowds altogether, and every example is collected the about 2ml of blood sample sample, and with phenol/chloroform drawer genomic dna, the extracting result detects with micro-ultraviolet spectrophotometer (INFINIGEN company).
Carry out the fluorescent PCR amplification by following system, at last with SDS 2.3 scanning and cluster analyses
| 384 orifice plates (ul) | |
| ??TaqMan?EXPress?Master?Mix(2X) | ??2.5 |
| ??20X?working?stock?of?SNP?Genotyping?Assay | ??0.25 |
| GDNA (about 3ng/ul) | ??2.25 |
| The reaction cumulative volume | ??5 |
Four, detected result;
The detected result of genome DNA extraction:
The genomic dna coincidence detection of all samples requires (260/280＞1.8, concentration＞10ng/ul, the detected result of No. 1175, sample as shown in Figure 1).
The detected result of AGTR1 gene rs388915 loci gene type
Embodiment 2
Detect the rs388915 site of essential hypertension susceptibility genes AGTR 1 with sequencing.Selecting each 10 example of above-mentioned hypertension case-control group sample checks order and judges the genotype of rs388915.
One, experimental technique
The PCR sequencing primer still adopts above-mentioned fluorescent PCR primer, the directly order-checking of the purified back of the product of amplification.The instrument of order-checking is the 3130xl genetic analyzer of ABI company, analyzes with sequence analysis 5.2 analysis software, and the result also can check with chromas.
Two, experimental result
The sequencing result sectional drawing as shown in Figure 2.
Finally, the gene type assay result of the sequencing result of 20 examples and 7900 fluorescent PCRs is in full accord.
Three, the association analysis of AGTR1 gene rs388915 genotype and hypertension susceptible
The relatively employing RxCx that AGTR1 gene rs388915 distributes in hypertensive patient and contrast
2Check. carry out statistical study with SPSS software, detected result and SPSS software analysis result are as shown in the table:
All quote proud reference in this application at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition read of the present invention above-mentioned tell about content after, those skilled in the art can make various changes or modification to the present invention, these forms fall within the application's appended claims institute restricted portion equally.
Claims (9)
1. the detection method of a hypertension susceptibility gene is characterized in that, detects the genotype in AGTR1 gene rs388915 site, and rs388915 has the hypertensive onset risk of the genotypic individuality of G and is significantly higher than the general population.
2. detection method as claimed in claim 1 is characterized in that the rs388915 site is positioned at AGTR1 gene intron 2.
3. detection method as claimed in claim 1 is characterized in that the method comprising the steps of:
(a) genomic dna of extracting sample, amplification obtains to comprise in the AGTR1 gene intron 2 zone in rs388915 site;
(b) genotype of mononucleotide polymorphism locus rs 388915 in detection step (a) product.
4. detection method as claimed in claim 3 is characterized in that, the primer sequence in zone that comprises the rs388915 site in the amplification AGTR1 gene intron 2 is shown in SEQ ID NO 2 and SEQ ID NO 3.
5. detection method as claimed in claim 3 is characterized in that, the genotypic probe sequence that detects rs388915 is shown in SEQ ID NO 4 and SEQ ID NO 5.
6. a test kit that detects hypertension susceptible gene is characterized in that, it contains and locus rs 388915 bonded probe.
7. test kit as claimed in claim 6 is characterized in that, with the sequence of locus rs 388915 bonded probe shown in SEQ ID NO:4 and SEQ ID NO:5.
8. test kit as claimed in claim 6 is characterized in that, it also comprises the primer that comprises the zone in rs388915 site in the specific amplification AGTR1 gene intron 2.
9. test kit as claimed in claim 8 is characterized in that, the sequence of primer in zone that comprises the rs388915 site in the specific amplification AGTR1 gene intron 2 is shown in SEQ ID NO:2 and SEQ ID NO:3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010217545XA CN101886129B (en) | 2010-06-30 | 2010-06-30 | Method for detecting mononucleotide polymorphism locus rs388915 of hypertension susceptibility genes AGTR 1 and detection kit |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010217545XA CN101886129B (en) | 2010-06-30 | 2010-06-30 | Method for detecting mononucleotide polymorphism locus rs388915 of hypertension susceptibility genes AGTR 1 and detection kit |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101886129A true CN101886129A (en) | 2010-11-17 |
| CN101886129B CN101886129B (en) | 2012-11-21 |
Family
ID=43072220
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010217545XA Expired - Fee Related CN101886129B (en) | 2010-06-30 | 2010-06-30 | Method for detecting mononucleotide polymorphism locus rs388915 of hypertension susceptibility genes AGTR 1 and detection kit |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101886129B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102876794A (en) * | 2012-09-29 | 2013-01-16 | 山东省皮肤病性病防治研究所 | Application of mononucleotide polymorphic rs6871626 in detection of susceptibility genes of lepriasis |
| CN103226667A (en) * | 2013-05-17 | 2013-07-31 | 西安时代基因健康科技有限公司 | Method for acquiring characterization parameters of hypertension and complication |
| CN107557432A (en) * | 2017-08-21 | 2018-01-09 | 上海派森诺医学检验所有限公司 | A kind of primer sets and detection kit for detecting hypertension medication related gene polymorphism |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004105145A (en) * | 2002-09-20 | 2004-04-08 | Japan Science & Technology Corp | Method for easily determining genetic risk of cardiovascular disease, obesity and life-style related disease |
| UA16183U (en) * | 2006-03-16 | 2006-07-17 | Ihor Petrovych Kaidashev | Method for pharmacogenetic selection of drugs for treating hypertension |
| CN1902327A (en) * | 2004-01-07 | 2007-01-24 | 中国医学科学院阜外心血管病医院 | Primary hypertension relative gene and its detecting method and usage |
| US20070092888A1 (en) * | 2003-09-23 | 2007-04-26 | Cornelius Diamond | Diagnostic markers of hypertension and methods of use thereof |
| CN101608219A (en) * | 2008-06-20 | 2009-12-23 | 上海主健生物工程有限公司 | Hypertension genetic test kit |
-
2010
- 2010-06-30 CN CN201010217545XA patent/CN101886129B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004105145A (en) * | 2002-09-20 | 2004-04-08 | Japan Science & Technology Corp | Method for easily determining genetic risk of cardiovascular disease, obesity and life-style related disease |
| US20070092888A1 (en) * | 2003-09-23 | 2007-04-26 | Cornelius Diamond | Diagnostic markers of hypertension and methods of use thereof |
| CN1902327A (en) * | 2004-01-07 | 2007-01-24 | 中国医学科学院阜外心血管病医院 | Primary hypertension relative gene and its detecting method and usage |
| UA16183U (en) * | 2006-03-16 | 2006-07-17 | Ihor Petrovych Kaidashev | Method for pharmacogenetic selection of drugs for treating hypertension |
| CN101608219A (en) * | 2008-06-20 | 2009-12-23 | 上海主健生物工程有限公司 | Hypertension genetic test kit |
Non-Patent Citations (2)
| Title |
|---|
| 《Hypertension》 19940731 Alain Bonnardeaux,et al Angiotensin II Type 1 Receptor Gene Polymorphisms in Human Essential Hypertension 63－69 1-9 第24卷, 第1期 2 * |
| 《J Hum Genet》 20071231 Norihisa Osawa,et al Combinational effect of genes for the renin-angiotensin system in conferring susceptibility to diabetic nephropathy 143-151 1－9 第52卷, 2 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102876794A (en) * | 2012-09-29 | 2013-01-16 | 山东省皮肤病性病防治研究所 | Application of mononucleotide polymorphic rs6871626 in detection of susceptibility genes of lepriasis |
| CN102876794B (en) * | 2012-09-29 | 2014-07-02 | 山东省皮肤病性病防治研究所 | Application of mononucleotide polymorphic rs6871626 in detection of susceptibility genes of lepriasis |
| CN103226667A (en) * | 2013-05-17 | 2013-07-31 | 西安时代基因健康科技有限公司 | Method for acquiring characterization parameters of hypertension and complication |
| CN103226667B (en) * | 2013-05-17 | 2016-05-25 | 西安时代基因健康科技股份有限公司 | The acquisition methods of the characterization parameter of hypertension and complication |
| CN107557432A (en) * | 2017-08-21 | 2018-01-09 | 上海派森诺医学检验所有限公司 | A kind of primer sets and detection kit for detecting hypertension medication related gene polymorphism |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101886129B (en) | 2012-11-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101892311B (en) | Detection method and kit of single nucleotide polymorphism locus rs7550536 of susceptibility gene of hypertension | |
| CN101892305B (en) | Method for detecting rs2295281 locus of hypertension susceptibility gene and detection kit | |
| CN101892302B (en) | Use and detection kit of locus rs2336384 of susceptibility gene of hypertension | |
| CN102586408B (en) | The detection method of hypertension susceptible gene Mfn2 mononucleotide polymorphism site rs3820189 and detection kit | |
| US10337004B2 (en) | Methods and compositions for treating a subject with a SMAD7 antisense oligonucleotide | |
| CN101886129B (en) | Method for detecting mononucleotide polymorphism locus rs388915 of hypertension susceptibility genes AGTR 1 and detection kit | |
| CN101892297B (en) | Detection method of single nucleotide polymorphism sites of hypertension susceptibility gene and kit thereof | |
| US20150057171A1 (en) | Oligonucleotides and methods for determining a predisposition to soft tissue injuries | |
| CN101886121B (en) | Method for detecting locus rs873457 of hypertension susceptibility genes and detection kit | |
| CN101886125A (en) | Method for detecting mononucleotide polymorphism locus rs2236058 of hypertension susceptibility genes and detection kit | |
| CN101892298B (en) | Method for detecting mononucleotide polymorphism rs2236055 locus of hypertension susceptibility gene and kit thereof | |
| CN101892296B (en) | Method for detecting hypertension susceptible gene and detection kit | |
| Kim et al. | Association between genetic polymorphism of multidrug resistance 1 gene and sasang constitutions | |
| CN101979657B (en) | Method and kit for detecting rs2878677 locus of susceptibility gene of hypertension | |
| CN101892303B (en) | Method for detecting rs4846085 locus of hypertension susceptibility gene and detection kit thereof | |
| CN101892301B (en) | Method for detecting hypertension susceptibility gene and detection kit | |
| CN104419759A (en) | Detection method and detection kit for single nucleotide polymorphism site rs7975232 of lung cancer susceptibility gene | |
| Duan et al. | Distributions of glucocorticoid receptor gene polymorphisms in a Chinese Han population and associations with outcome after major trauma | |
| CN101805784B (en) | Single nucleotide polymorphism of human WNK4 genes and application thereof | |
| CN105603053A (en) | High blood pressure susceptible gene SCN7A single nucleotide polymorphism site rs7565062 detection kit | |
| CN102732602A (en) | Method for detecting gene rs2255390 site of hypertension susceptible gene WNK1 and detection kit thereof | |
| CN104450690A (en) | Primary hypertension susceptibility gene variation locus and detecting method thereof | |
| CN104450688A (en) | Hypertension susceptibility relevant gene variation locus and detecting method thereof | |
| CN104450884A (en) | Hypertension susceptibility relevant gene variation locus and detecting method thereof | |
| Limou et al. | Identification of an IL-7RA risk allele for rapid progression to AIDS: Results of a genomic IL-7/IL-7RA study in the GRIV cohort |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121121 Termination date: 20170630 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |