CN101857899A - Kit for detecting senile macular degeneration disease - Google Patents
Kit for detecting senile macular degeneration disease Download PDFInfo
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- CN101857899A CN101857899A CN 201010162728 CN201010162728A CN101857899A CN 101857899 A CN101857899 A CN 101857899A CN 201010162728 CN201010162728 CN 201010162728 CN 201010162728 A CN201010162728 A CN 201010162728A CN 101857899 A CN101857899 A CN 101857899A
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Abstract
The invention provides a kit for detecting senile macular degeneration disease, comprising a related reagent selected freely from rs1061170 variation of exon 9, rs1329428 variation of intron 15, rs800292 variation of exon 2 used for detecting CFH gene and/or rs3753394 variation in a 5' non-coding region used for AMD screening diagnosis. By detecting whether the above locus has variation or not, the kit can detect that risk of senile macular degeneration disease has high association with AMD, and can be used for monitoring and detecting AMD high risk group at an early stage so as to implement early-stage prevention and curing and reduce vision damage to AMD high risk group.
Description
Technical field
The present invention relates to a kind of test kit that detects agedness yellow spot degenerative disease, specifically detect the test kit of relevant CFH genovariation with agedness yellow spot degenerative disease.
Background technology
It is the different substantiality disease of feature with decline of carrying out property central vision and the retinal pigment epithelium sex change of macula lutea portion that macular degeneration disease is considered to a class, is important blinding illness in eye.Macular degeneration comprises age-related macular degeneration, macular dystrophy (stargart disease, best disease, sorsby fundus dystrophy etc.).Age-related macular degeneration (age-related macular degeneration, AMD) now become one of topmost blinding illness in eye of the elderly, whole world number of patients 1,000 ten thousand, China 60-69 year crowd AMD morbidity is can reach 15.33% more than 7.77%, 70 years old.Also do not have effective methods of treatment for AMD at present, its major cause is exactly that pathogenesis it be unclear that.
Recent study thinks that macular degeneration is one group of different substantiality disease, and inherited genetic factors plays an important role in its pathogenesis.Some have similar research clinical and the other types macular degeneration that histopathology shows to make important progress to age-related macular degeneration (AMD), such as: discover that in recent years recessive Stargardt macular degeneration has variation on the ABCR gene; Dominance Stargardt macular degeneration (STGD3) has variation on the ELOVL4 gene; Best macular dystrophy (BMD) has variation on the VMD2 gene; There is the some variation in Sorsby fundus dystrophy patient at the TIMP3 gene, also has macula lutea butterfly sample atrophy etc. relevant with Peripherin/RDS genovariation.
Senile macular degeneration SMD is the major cause that causes developing country's non-reversibility visual loss, studies show that much it has significant genetic predisposition.At the research of different crowd, just becoming one of international research focus at present with race's macular degeneration disease.The real as yet systematicness of domestic monogenic macular degeneration disease and disease crowd and the ethnic contrast crowd's that is complementary genetic analysis (multigenic disease analysis) work is carried out, and does not also have relevant gene profile analysis.
The early-stage Study of AMD confirms alternative pathway of complement member's encoding gene, comprises that complement factor H (CFH) and factor B/C2 are relevant with individual ill risk, and the CFH that especially is positioned on the karyomit(e) 1q31 is considered to the main risks and assumptions of AMD.Some other association analysis shows that also karyomit(e) 10q26 goes up the risk site that has another AMD.Yet its definite Disease-causing gene it be unclear that.
Age-related macular degeneration is a kind of retinopathy of the multifactor compound action relevant with age growth.Mostly occur more than 45 years old, the age is big more, and morbidity is high more.It is one of primary disease of whole world adult's blinding.Senile macular degeneration SMD develops very slow sometimes, makes the patient be difficult for discovering, and but makes much progress sometimes, deprive the patient rapidly and look the thing ability, thereby its early discovery and prevention seems most important.
The real etiology unknown of this disease is a multi-factor disease, and influence factor also has ethnic group, sex, metabolism etc. except that the age, and inherited genetic factors is most important.Be divided into atrophic type (dryness type) and exudative type (moist type) clinically.Dryness person, visible glassy membrane wart progressively causes the macular area attenuation on the eyeground, thereby influences function.Still there is not special effective means treatment at present.Moist person causes the serious hindrance of eyesight more, and its eyesight destructive reason mainly is that unusual new vessel is grown under retina, causes the destruction of retinal hemorrhage, oedema and retinal tissue, finally causes cicatrization, thereby causes the forfeiture of eyesight.Moist AMD is morbidity in a single day, and the course of disease is rapid, and the poor effect of conventional treatment is difficult to recover significantly the visual function that it has been lost.Therefore, early diagnosis is found, intervenes early, can better delay the course of disease, reduces patient's visual loss, improves the quality of living.
Present AMD diagnoses in dependence: 1, more than the elderly's morbidity more than 50 years old, the age is big more, and sickness rate is high more; 2, metamorphopsia, visual deterioration or obvious visual disorder successively take place in eyes; 3, there are significantly glassy membrane wart and amphitypy performance separately in the eyeground; 4, fluorescence fundus angiography.But, lack the monitoring, diagnosing index at patient's their early stage, utilize the genetic marker of this research, can find AMD high risk population by early screening, and implement early detection and prevention, reduce its inpairment of vision.
Summary of the invention
The object of the present invention is to provide the test kit that detects agedness yellow spot degenerative disease, thereby this test kit derives from whether there is CFH genovariation (single nucleotide polymorphism SNPrs1061170, rs1329428, rs800292, rs3753394) in the sample of individuality to be measured the generation of monitoring or diagnosis agedness yellow spot degenerative disease in early days by detection, and then provides reference for clinical diagnosis and treatment.
The susceptibility loci that the present invention is directed to 1q32 karyomit(e) CFH gene has carried out the gene type assay of AMD and normal control, the a plurality of SNP variations of discovery between the CFH gene are the important causes of disease that cause Chinese AMD, these variations SNP comprises the rs800292 (G/A) of the rs1329428 (G/A) of the rs1061170 (C/T) that is positioned at No. 9 exons, No. 15 introns, No. 2 exons, the rs3753394 (T/C) of 5` non-coding region, and the present invention has found the direct correlation of these variations and Chinese AMD first in the whole nation.
According to an aspect of the present invention, be provided for detecting the test kit of agedness yellow spot degenerative disease, whether the detection principle of test kit exists for detecting with the closely-related CFH genovariation of agedness yellow spot degenerative disease, can comprise in the test kit being used to detect the reagent that the CFH gene SNP site relevant with Chinese AMD pathology comprises rs1061170, rs1329428, rs800292, rs3753394.At first increase to the sample extraction DNA of acquisition and at the rs800292 (G/A) of the rs1329428 (G/A) of the rs1061170 (C/T) of No. 9 exons of CFH gene, No. 15 introns, No. 2 exons, rs3753394 (T/C) site of 5` non-coding region, detection method can be with reference to the method in detection point mutation well known to those skilled in the art site, for example direct sequencing or use the restriction fragment length polymorphism method or single base primers extension method or Taqman method or chip hybridization etc. is judged the allelotype in these SNP sites.
According to a further aspect in the invention, also provide the rs800292 variation of the rs1329428 variation of the rs1061170 variation of No. 9 exons of CFH gene, No. 15 introns, No. 2 exons and/or the rs3753394 variation of 5` non-coding region to be used for the application that AMD screens diagnostic reagent in preparation.
Particularly, described screening diagnostic reagent comprises that A → G of the rs800292 of A → G variation of the rs1329428 of T → C variation of the rs1061170 that detects No. 9 exons of CFH gene, No. 15 introns, No. 2 exons makes a variation and/or the reagent of C → T variation of the rs3753394 of 5` non-coding region; And the reagent of the rs3753394 gene fragment of the rs800292 of optional be used to the increase rs1329428 of the rs1061170 that comprises No. 9 exons of CFH gene, No. 15 introns, No. 2 exons and/or 5` non-coding region.
More specifically, the T of the rs1061170 of No. 9 exons of described detection CFH gene → C variation, the A of the rs1329428 of No. 15 introns → G variation, the reagent of the C of the rs3753394 of the A of the rs800292 of No. 2 exons → G variation and/or 5` non-coding region → T variation is order-checking reagent, restriction fragment length polymorphism method reagent, Snapshot reagent and digestion with restriction enzyme method, sex change high performance liquid chromatography (DHPLC method), Taqman real-time fluorescence quantitative PCR method, special primer PCR method (ASO) or based on the chip detecting method reagent of allele specific oligonucleotide hybridization principle.
The invention provides the test kit that detects agedness yellow spot degenerative disease, can be used for early stage monitoring and detect AMD high risk population, implement early prevention and treatment, reduce its inpairment of vision.Test kit of the present invention sports target with a plurality of SNP that are associated with AMD in the CFH gene and works in coordination with detection, more can improve the accuracy of detection.
Description of drawings:
Fig. 1 is the genotype figure that Snapshot detects SNP rs1061170/rs1329428/rs800292/rs3753394
The embodiment of invention
[embodiment 1] blood sample collection and sample disposal
Choose 240 routine Chinese's senile macular degeneration SMD (AMD) patient and 250 routine collators.The patient is the AMD of clinical definite, wherein
160The moist AMD patient of example,
80Example dryness AMD patient, contrast is the crowd who changes more than or equal to 60 years old, non-glass wart and retinochrome who meets AMD patient age section.
To all its medical history of participator's probe and family history, and it is carried out a medical examination and detailed ophthalmology training inspection.Everyone gathers EDTA anti-freezing blood sample 5～10ml after the signature Informed Consent Form.Phenol-chloroform method extracts genomic dna.
[embodiment 2] comprise the pcr amplification and the gene type assay of rs1061170, rs1329428, rs800292, rs3753394 single nucleotide polymorphism dna fragmentation
1, extracts the poba gene group DNA of AMD patient and control group.
2, the pcr amplification genome comprises the genomic DNA fragment of aim sequence (rs1061170, rs1329428, rs800292, rs3753394)
Primer sequence:
Rs1061170: forward: 5 '-TGGTCCTTAGGAAAATGT-3 '
Oppositely: 5 '-GCTTTTGGAAGAGCGTAG-3 '
Rs1329428: forward: 5 '-GGCTCACCCCAGTGATACAT-3 '
Oppositely: 5 '-AACAGGGGAGCTGCATTTTA-3 '
Rs800292: forward: 5 '-CCATTCTCCCTTCCTGCATA-3 ';
Oppositely: 5 '-GATTGCAATGAACTTCCTCCA-3 '
Rs3753394: forward: 5 '-CCCCAAATTCATCAAGCACT-3 ';
Oppositely: 5 '-TAGGGAAATTCTCCGTTGGA-3 '
Reaction conditions:
rs1061170：95℃3minutes，(94℃30seconds，50℃30seconds，72℃45seconds)*35cycles?72℃10minutes?4℃forever
rs1329428：95℃3minutes，(94℃30seconds，51℃30seconds，72℃45seconds)*35cycles?72℃10minutes?4℃forever
rs800292：95℃3minutes，(94℃30seconds，53℃30seconds，72℃45seconds)*35cycles?72℃10minutes?4℃forever
rs3753394：95℃3minutes，(94℃30seconds，53℃30seconds，72℃45seconds)*35cycles?72℃10minutes?4℃forever
3, the gene type assay of sample
(1) single base primers extension method gene type (SnapShot)
1. purifying PCR reaction product
Reaction system:
Annotate: PCR product cumulative volume 9 μ l decide on PCR reaction quantity, and N is to the PCR of primer, and then the product application of sample of every pair of primer acquisition is 9 μ l/N.
Reaction conditions: 37 ℃ of 1hour; 75 ℃ of 15min
2. single base primers extends
Reaction system:
Reaction conditions: 96 ℃ of 1min
The snpshot primer:
rs1329428：TTTCATTCAG?GGACTGTATT?CTAAA(25bp)
rs1061170：ATTTT?CCTTATTTGG?AAAATGGATA?TAATCAAAAT(35bp)
rs800292：ATGGATTA?AGAGCAACCC?ATTCTCCCTT?CCTGCATACC?ATTATTA(45bp)
rs3753394：AATAGAC?CCGAATAGAG?TTTGAATAAT?TGAAGGGTTT?ATGAAATCCA
GAGGATAT(55bp)
3. purification reaction thing
Reaction system: 0.7 μ l SAP/well
Reaction conditions: 37 ℃ of 1hour; 75 ℃ of 15min
4. sex change
Reaction system:
Reaction conditions: 95 ℃ of 5min; Ice bath cooling rapidly
5.ABI3100 go up the machine-readable genotype result that gets
(2) nucleotide sequencing
1, glue reclaims:
(1) will be placed with and add Binding Buffer30ulfangru in the pipe that glue reclaims and hatch 7min for 55 ℃.
(treating to dissolve fully)
(2) after the peptizationization, take out column jecket, perform mark, liquid is changed in the column jecket, 10000rpm/1min is centrifugal, outwells supernatant liquor after finishing, and adds 700ulSpw again, leaves standstill 2 ~ 3min, and 10000rpm/1min is centrifugal, outwells supernatant liquor.
(3) repeat above-mentioned 2 operations once.
(4) outwell supernatant liquor after, column jecket 1000rpm/1min is dallied.
(5) add 15ulElution Buffer to post central authorities, leave standstill 2 ~ 3min, 10000rpm/1min is centrifugal.
(6) repeat aforesaid operations
(7) liquid light that elutes is gone in the clean pipe, perform mark, place refrigerator.
2, amplification before the order-checking
Reaction system:
Reaction conditions:
3, the second step purifying:
4, go up the machine order-checking
1ul/well behind the mixing, the 25ul dehydrated alcohol/wel 15min that keeps in Dark Place, 4100rpm/30min is centrifugal.Blot supernatant liquor as far as possible, 70% ethanol 40ul/well, 4100rpm/10min is centrifugal..Blot supernatant liquor, the room temperature 15min that keeps in Dark Place.Add 9ul/well, lucifuge is placed 1hour.
(3) additive method
1, based on the chip detection of allele specific oligonucleotide hybridization principle
------------------------------dyeing----scans----data analysis to chip hybridization to biotin labeling to the product fragmentation to flow process: DNA extracting in washing in amplification to add joint in DNA digestion
2, Tagman method
Flow process: sequence alignment----design of primers----primer is synthetic----DNA extracting and quantitatively--PCR---probe hybridization----scanning----analysis
3, sex change high performance liquid chromatography (Denature HPLC)
Fig. 1 detects the genotype figure of SNP rs1061170, rs1329428, rs800292, rs3753394 for Snapshot, among the figure, rs1329428 is heterozygote A/G, and rs1061170 is heterozygote C/T, rs800292 is heterozygote G/A, and rs3753394 is heterozygote C/T.Rs1329428 homozygote GG, rs1061170 homozygote CC, rs800292 homozygote GG, rs3753394 homozygote TT and ill risk positive correlation.
The correlation analysis result of [embodiment 3] CFH gene mononucleotide polymorphism and AMD
Adopt chi square test to analyze the allelotrope dependency, calculate odds ratio and 95% credibility interval simultaneously, estimated risk allelotrope and ill risk relation (OR value representation).Band " * " base is a risk genes in the table.
The correlation analysis result of [embodiment 4] CFH gene haplotype polymorphism and AMD
Utilize software HaploView to CFH gene monoploid polymorphism (rs3753394; rs800292, rsi061170and rs1329428) can find with the correlation analysis of AMD: haplotype CATA is that a kind of protection type haplotype and AMD have close association (seeing the following form).Thereby can find by screening agent and may suffer from AMD low risk individuality.
[embodiment 5] test kit
This test kit is used for: 1, AMD patient's early diagnosis and somatotype reference; 2, the gene test of AMD Susceptible population and risk assessment.
[reagent]
[operation steps]
Rs1061170; S1329428; Rs800292; Rs3753394
Pcr amplification and gene type assay:
1. sampling: get patient's whole blood (EDTA anti-freezing) 1ml, extract AMD patient's poba gene group DNA.
2.PCR operation: genomic dna 1ul+9ul PCR mixed solution
Reaction conditions:
rs1061170/rs1329428：
95℃3minutes，(94℃30seconds，50℃30seconds，72℃45seconds)
*35?cycles?72℃?10minutes?4℃?forever
rs800292/rs3753394：
95℃3minutes，(94℃30seconds，53℃30seconds，72℃45seconds)
*35?cycles?72℃?10minutes?4℃forever
3, PCR product purification
Reaction system:
| PCR product cumulative volume | 1-9μl |
| The Exol enzyme | 0.1μl |
| ?SAP?buffer | 0.1μl |
| ?SAP | 2μl |
| DdH2O supplies cumulative volume | 12μl |
Annotate: PCR product cumulative volume is looked PCR production concentration decision consumption.
Reaction conditions:
4, single base primers extends
Reaction system:
| Purified product | ?1μl |
| SNaPshot?Multiplex | ?1μl |
| SNaPshot?primer | ?0.2×N |
| DdH2O | Supply 5 μ l |
Reaction conditions:
The snpshot primer:
rs1329428：TTTCATTCAG?GGACTGTATT?CTAAA(25bp)
rs1061170：ATTTT?CCTTATTTGG?AAAATGGATA?TAATCAAAAT(35bp)
rs800292：ATGGATTA?AGAGCAACCC?ATTCTCCCTT?CCTGCATACC?ATTATTA(45bp)
rs3753394：AATAGAC?CCGAATAGAG?TTTGAATAAT?TGAAGGGTTT?ATGAAATCCA
GAGGATAT(55bp)
5, purification reaction thing
Reaction system: 0.7 μ l SAP/well
Reaction conditions: 37 ℃ of 1hour; 75 ℃ of 15min
6, the ABI genetic analyzer reads the result
Reaction system: purified product 1 μ l+HD 9 μ l
Reaction conditions: 95 ℃ of 5min; Ice bath cooling rapidly.
The last machine-readable genotype result that gets of ABI3100
[result's judgement]
SEQUENCE?LISTING
＜110〉Medical Scientific Academy in Sichuan(Sichuan People's Hospital)
＜120〉detection kit of agedness yellow spot degenerative disease
<130>CD537-10P108121
<150>200910058838.5
<151>2009-04-03
<160>12
<170>PatentIn?version?3.2
<210>1
<211>18
<212>DNA
＜213〉forward primer of amplification rs1061170
<400>1
tggtccttag?gaaaatgt?????????????????????????????????????????????18
<210>2
<211>18
<212>DNA
＜213〉reverse primer of amplification rs1061170
<400>2
gcttttggaa?gagcgtag?????????????????????????????????????????????18
<210>3
<211>20
<212>DNA
＜213〉forward primer of amplification rs1329428
<400>3
ggctcacccc?agtgatacat???????????????????????????????????????????20
<210>4
<211>20
<212>DNA
＜213〉reverse primer of amplification rs1329428
<400>4
aacaggggag?ctgcatttta???????????????????????????????????????????20
<210>5
<211>20
<212>DNA
＜213〉forward primer of amplification rs800292
<400>5
ccattctccc?ttcctgcata???????????????????????????????????????????20
<210>6
<211>21
<212>DNA
＜213〉reverse primer of amplification rs800292
<400>6
gattgcaatg?aacttcctcc?a?????????????????????????????????????????21
<210>7
<211>20
<212>DNA
＜213〉forward primer of amplification rs3753394
<400>7
ccccaaattc?atcaagcact???????????????????????????????????????????20
<210>8
<211>20
<212>DNA
＜213〉reverse primer of amplification rs3753394
<400>8
tagggaaatt?ctccgttgga???????????????????????????????????????????20
<210>9
<211>25
<212>DNA
＜213〉the snpshot primer of rs1329428
<400>9
tttcattcag?ggactgtatt?ctaaa?????????????????????????????????????25
<210>10
<211>35
<212>DNA
＜213〉the snpshot primer of rs1061170
<400>10
attttcctta?tttggaaaat?ggatataatc?aaaat??????????????????????????35
<210>11
<211>45
<212>DNA
＜213〉the snpshot primer of rs800292
<400>11
atggattaag?agcaacccat?tctcccttcc?tgcataccat?tatta???????????????45
<210>12
<211>55
<212>DNA
＜213〉the snpshot primer of rs3753394
<400>12
aatagacccg?aatagagttt?gaataattga?agggtttatg?aaatccagag?gatat????55
Claims (11)
1. be used to detect the test kit of agedness yellow spot degenerative disease, comprise that optional being used to detects the rs800292 variation of the rs1329428 variation of the rs1061170 variation of No. 9 exons of CFH gene, No. 15 introns, No. 2 exons and/or the rs3753394 variation of 5` non-coding region is used for the related reagent that AMD screens diagnosis.
2. the described test kit of claim 1, it is characterized in that described test kit comprises that A → G of the rs800292 of A → G variation of the rs1329428 of T → C variation of the rs1061170 that detects No. 9 exons of CFH gene, No. 15 introns, No. 2 exons makes a variation and/or the reagent of C → T variation of the rs3753394 of 5` non-coding region; And the reagent of the rs3753394 gene fragment of the rs800292 of optional be used to the increase rs1329428 of the rs1061170 that comprises No. 9 exons of CFH gene, No. 15 introns, No. 2 exons and/or 5` non-coding region.
3. the described test kit of claim 2 is characterized in that A → G of the rs1329428 of T → C variation of the rs1061170 of No. 9 exons of described detection CFH gene, No. 15 introns makes a variation, A → G of the rs800292 of No. 2 exons makes a variation and/or the reagent of the C of the rs3753394 of 5` non-coding region → T variation is order-checking reagent.
4. the described test kit of claim 2 is characterized in that A → G of the rs800292 of A → G variation of the rs1329428 of T → C variation of the rs1061170 of No. 9 exons of described detection CFH gene, No. 15 introns, No. 2 exons makes a variation, the reagent of the C of the rs3753394 of 5` non-coding region → T variation is restriction fragment length polymorphism method reagent.
5. the described test kit of claim 2 is characterized in that A → G of the rs800292 of A → G variation of the rs1329428 of T → C variation of the rs1061170 of No. 9 exons of described detection CFH gene, No. 15 introns, No. 2 exons makes a variation, the reagent of the C of the rs3753394 of 5` non-coding region → T variation is Snapshot reagent.
6.CFH the rs800292 variation of the rs1329428 variation of the rs1061170 of No. 9 exons of gene variation, No. 15 introns, No. 2 exons and/or the rs3753394 variation of 5` non-coding region are used for the application of AMD screening diagnostic reagent in preparation.
7. application according to claim 6 is characterized in that described screening diagnostic reagent comprises that A → G of the rs800292 of A → G variation of the rs1329428 of T → C variation of the rs1061170 that detects No. 9 exons of CFH gene, No. 15 introns, No. 2 exons makes a variation and/or the reagent of C → T variation of the rs3753394 of 5` non-coding region; And the reagent of the rs3753394 gene fragment of the rs800292 of optional be used to the increase rs1329428 of the rs1061170 that comprises No. 9 exons of CFH gene, No. 15 introns, No. 2 exons and/or 5` non-coding region.
8. application according to claim 7 is characterized in that A → G of the rs1329428 of T → C variation of the rs1061170 of No. 9 exons of described detection CFH gene, No. 15 introns makes a variation, A → G of the rs800292 of No. 2 exons makes a variation and/or the reagent of the C of the rs3753394 of 5` non-coding region → T variation is order-checking reagent.
9. application according to claim 7 is characterized in that A → G of the rs1329428 of T → C variation of the rs1061170 of No. 9 exons of described detection CFH gene, No. 15 introns makes a variation, A → G of the rs800292 of No. 2 exons makes a variation and/or the reagent of the C of the rs3753394 of 5` non-coding region → T variation is restriction fragment length polymorphism method reagent.
10. application according to claim 7 is characterized in that A → G of the rs1329428 of T → C variation of the rs1061170 of No. 9 exons of described detection CFH gene, No. 15 introns makes a variation, A → G of the rs800292 of No. 2 exons makes a variation and/or the reagent of the C of the rs3753394 of 5` non-coding region → T variation is Snapshot reagent.
11. application according to claim 7, the reagent of C → T variation that it is characterized in that the rs3753394 of the A → G variation of the rs800292 of A → G variation of the rs1329428 of T → C variation of the rs1061170 of No. 9 exons of described detection CFH gene, No. 15 introns, No. 2 exons and/or 5` non-coding region are digestion with restriction enzyme method, sex change high performance liquid chromatography, Taqman real-time fluorescence quantitative PCR method, special primer PCR method or based on the chip detecting method reagent of allele specific oligonucleotide hybridization principle.
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Cited By (8)
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| CN103215265A (en) * | 2012-05-14 | 2013-07-24 | 四川省医学科学院（四川省人民医院） | Screening kit for age-related macular degenerative disease |
| CN103562408A (en) * | 2011-03-15 | 2014-02-05 | 犹他大学研究基金会 | Methods of diagnosing and treating vascular associated maculopathy and symptoms thereof |
| CN106222253A (en) * | 2016-03-21 | 2016-12-14 | 四川省人民医院 | The detection kit of age-related macular degeneration choroid polypoid vascular lesion disease |
| CN109119165A (en) * | 2018-08-27 | 2019-01-01 | 珠海为凡医疗信息技术有限公司 | A kind of prevalence of cataract risk checking method, device and electronic equipment |
| CN109585017A (en) * | 2019-01-31 | 2019-04-05 | 上海宝藤生物医药科技股份有限公司 | A kind of the risk prediction algorithms model and device of age-related macular degeneration |
| CN109706238A (en) * | 2017-10-26 | 2019-05-03 | 珠海岐微生物科技有限公司 | A kind of detection and treatment method for the treatment of senile maculopathy |
| CN113293206A (en) * | 2021-07-23 | 2021-08-24 | 西安医臻生物医药科技有限公司 | Method for rapidly identifying risk of age-related macular degeneration and application |
| CN113718025A (en) * | 2021-09-01 | 2021-11-30 | 桂林医学院附属医院 | KASP-based SNP kit for detecting diabetic retinopathy gene |
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