CN107885970A - Drug metabolic enzyme metabolic pattern appraisal procedure - Google Patents
Drug metabolic enzyme metabolic pattern appraisal procedure Download PDFInfo
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Abstract
The present invention provides a kind of drug metabolic enzyme metabolic pattern appraisal procedure, including step：S1：Named from the haplotype Variant allele of default gene database acquisition gene and form gene information table；S2：Double form variation type allele name sequence is obtained according to gene information table；S3：Form metabolic pattern and obtain metabolic pattern information table；S4：The double type name table in site is obtained according to genetic test result；S5：Obtain the first haplotype Variant allele name sequence；S6：Second haplotype Variant allele name sequence is obtained according to each haplotype Variant allele enzymatic activity；S7：Double form variation type allele name result is obtained from the second haplotype Variant allele name sequence；S8：Metabolic pattern testing result is obtained from the table search of metabolic pattern information.A kind of drug metabolic enzyme metabolic pattern appraisal procedure of the present invention, can accurate judgement gene metabolic pattern, have significance in terms of drug metabolic enzyme genetic test and personalized medicine.
Description
Technical field
The present invention relates to technical field of gene detection, more particularly to a kind of drug metabolic enzyme metabolic pattern appraisal procedure.
Background technology
In pharmacogenetics, most widely used nomenclature describes pharmacogenetics genotype and is different from other science of heredity bases
Because of detection, such as metabolism related gene cytochromes p450 families, Human cytochrome P450 (CYP) allele name committee
Member's meeting (http://www.cypalleles.ki.se) recommend to be named with " * ", refer to Fig. 1.Within the system, it is most common
Allele is designated as " * 1 ".Substantially, " * " allele is the combined result that multiple base positions are undergone mutation.
At present, either gene sequencing technology or SNP (SNP) chip is detected, and multiple sites can only be carried out respectively
The Genotyping (genotype) of independence judges, and the SNP site that can not specifically judge to occur is cis, i.e., in same
Chromosome；Or it is trans, that is, appear in different chromosome.Therefore can not also " * " allele be carried out to the gene of detection
Name.
Drug metabolism in vivo, transhipment and the hereditary variation of drug target point gene and its change of expression can pass through
Concentration and sensitiveness inside medicine are influenceed, causes drug responsiveness individual difference.Recently as the hair of human activities environment
Exhibition, pharmacogenomics field has obtained fast development, increasing Drug Discovery biomarker and its detection method
Emerge in large numbers in succession.Pharmacogenomics has turned into be instructed clinical individual medication, assesses severe drug adverse reaction occurrence risk, refers to
Lead new drug development and evaluate the important tool of new drug, the new drug of part listing is only limitted to the eligible patients of specific gene type.Mesh
Before, the research on drug metabolism enzymatic activity, which is mainly derived from, to be studied the external activity of its allelotype (" * " is named).
The content of the invention
For above-mentioned deficiency of the prior art, the present invention provides a kind of drug metabolic enzyme metabolic pattern appraisal procedure, can be accurate
Really judge the metabolic pattern of the gene, this is significant in terms of drug metabolic enzyme genetic test with personalized medicine.
To achieve these goals, the present invention provides a kind of drug metabolic enzyme metabolic pattern appraisal procedure, including step：
S1：The life of the haplotype Variant allele in the multiple sites of a target gene is obtained from a default gene database
Name and gene information, and the gene information will be associated with the name of the corresponding haplotype Variant allele,
Obtain a gene information table；
S2：The a pair of of the target gene is obtained according to the name permutation and combination of each haplotype Variant allele
Times form variation type allele name sequence, the double form variation type allele name sequence include the target gene
All names of double form variation type allele；
S3：Each double form variation type allele is determined according to the enzymatic activity of the haplotype Variant allele
Metabolic pattern, and the name of the metabolic pattern and the corresponding double form variation type allele is associated, obtains a metabolic pattern
Information table；
S4：Obtained according to the genetic test result in the multiple site of the target gene and the gene information table
The name of the double form variation type allele in each site and by the life of the double form variation type allele
Name associates with the site, obtains the double type name table in a site；
S5：From the site, double type name table extracts the life of all haplotype Variant alleles in each site
Name, obtain one first haplotype Variant allele name sequence；
S6：According to the enzymatic activity of each haplotype Variant allele from low to high successively to first haplotype
The name of each haplotype Variant allele is ranked up in Variant allele name sequence, and it is single to obtain one second
Times form variation type allele name sequence；
S7：Choose most the first two haplotype anomaly equipotential of the second haplotype Variant allele name sequence
Unnamed gene forms the name result of a double form variation type allele of the target gene；
S8：According to the name result of the double form variation type allele one is obtained from the metabolic pattern information table search
Metabolic pattern testing result.
Preferably, in the S1 steps, the gene information includes：Gene Name, with reference to base and mutating alkali yl；It is described
Gene information table includes the name of the gene information, site information and the haplotype Variant allele.
Preferably, the default gene database includes pharmGKB databases and Human cytochrome P450 equipotential base
Because of naming committee database.
Preferably, in the S3 steps, the metabolic pattern of the double form variation type allele includes：Ultra-rapid metabolism type,
Fast metabolic pattern, intermediate supersession type and weak metabolic pattern.
Preferably, in the S4 steps, the genetic test result includes the Gene Name, the site information and inspection
Cls gene type information.
Preferably, the genetic test result is obtained by gene sequencing or genechip detection.
The present invention makes it have following beneficial effect as a result of above technical scheme：
The method of the present invention can cause the power of proteinase activity according to different pharmaceutical metabolic enzyme gene SNP site, pass through
Algorithm come estimate SNP site combination caused by Variant allele name.Due to Variant allele and protein active
There is stronger corresponding relation, can be used directly to judge the metabolic pattern of detection people's drug metabolic enzyme, be a kind of by drug metabolic enzyme
The method that typing gene polymorphisms data are mapped to enzymatic activity metabolism parting, personalized medicine side is being instructed according to genetic test
Mask is significant；With the advantages of accuracy in detection is high, detection process is convenient and detection efficiency is high.
Brief description of the drawings
Fig. 1 is cromoci YP2D6 allele Naming conventions schematic diagram in the prior art；
Fig. 2 is the flow chart of the drug metabolic enzyme metabolic pattern appraisal procedure of the embodiment of the present invention.
Embodiment
Below according to accompanying drawing 2, presently preferred embodiments of the present invention is provided, and is described in detail, makes to be better understood when this
Function, the feature of invention.
Referring to Fig. 2, a kind of drug metabolic enzyme metabolic pattern appraisal procedure of the embodiment of the present invention, including step：
S1：The life of the haplotype Variant allele in the multiple sites of a target gene is obtained from a default gene database
Name and gene information, in the present embodiment, the name of haplotype Variant allele be labeled as Ci, 1≤i≤n, n for it is single again
The number of form variation type allele；And will be related to the name of corresponding haplotype Variant allele by gene information
Connection, obtain a gene information table.Wherein, presetting gene database includes pharmGKB databases and Human cytochrome P450 etc.
Position unnamed gene committee database；Gene information includes：Gene Name, with reference to base and mutating alkali yl；Gene information table bag
Include the name of gene information, site information and haplotype Variant allele.
S2：A double form variation of target gene is obtained according to the name permutation and combination of each haplotype Variant allele
Type allele names sequence, and double form variation type allele name sequence includes the double form variation type of whole of target gene
The name of allele.
S3：The metabolism of each double form variation type allele is determined according to the enzymatic activity of haplotype Variant allele
Type, and metabolic pattern is associated with the name of corresponding double form variation type allele, obtain a metabolic pattern information table；Double type becomes
The metabolic pattern of special-shaped allele includes：Ultra-rapid metabolism type (UM), fast metabolic pattern (EM), intermediate supersession type (IM) and weak metabolic pattern
(PM)。
S4：The double type in each site is obtained according to the genetic test result in multiple sites of target gene and gene information table
The name of Variant allele simultaneously associates the name of double form variation type allele with site, obtains the double type in a site
Name table；Genetic test result includes Gene Name, site information and detection genotype information.Genetic test result passes through gene
Sequencing or genechip detection obtain.
Wherein, when the result for detecting some site is heterozygous, the double form variation type allele mark in the site
For * 1/Ci；If testing result is homozygous mutant, Ci/Ci is designated as；If testing result is homozygous wildtype, * 1/*1 are designated as.
S5：From site, double type name table extracts the name of all haplotype Variant alleles in each site, obtains
One first haplotype Variant allele names sequence；
S6：According to the enzymatic activity of each haplotype Variant allele from low to high successively to first haplotype anomaly etc.
The name of each haplotype Variant allele is ranked up in the unnamed gene sequence of position, obtains one second haplotype anomaly etc.
Position unnamed gene sequence；When the enzymatic activity height of two haplotype Variant alleles can not determine, two haplotype is set
The enzymatic activity of Variant allele is consistent.
S7：Choose most the first two haplotype Variant allele of the second haplotype Variant allele name sequence
The name result of one double form variation type allele of name composition target gene；
S8：The inspection of one metabolic pattern is obtained from the table search of metabolic pattern information according to the name result of double form variation type allele
Survey result.
Such as：By taking drug metabolic enzyme CYP2D6 as an example, the mutational site on CYP2D6 genes is currently known more than 150
Individual, corresponding Variant allele name is also above 100 kinds.According to mutational site in the frequency of mutation of asian population, selection
Wherein 3 sites, are made a concrete analysis of.With the genetic test result containing this 3 sites of CYP2D6 genes, as shown in table 1.
The genetic test result table of table 1.
| Gene Name | Detection site | Testing result |
| CYP2D6 | rs1065852 | GA |
| CYP2D6 | rs5030865 | TT |
| CYP2D6 | rs16947 | GG |
First, according to PharmGKB databases, the gene information table of CYP2D6 3 target sites of allele is built, such as
Shown in Fig. 2.
The gene information table of table 2.
| Gene Name | Site | With reference to base | Mutating alkali yl | Haplotype |
| CYP2D6 | rs1065852 | G | A | *10 |
| CYP2D6 | rs5030865 | C | T | *14 |
| CYP2D6 | rs16947 | G | A | *2 |
Then, according to Human cytochrome P450 (CYP) allele naming committee database (http:// www.cypalleles.ki.se), CYP2D6 allele activity sorting data forms are obtained, wherein, the anomaly of haplotype
The enzymatic activity (IC50) of allele it is minimum be " 1 ", it is incremented by successively, in CYP2D6 allele activity sorting data forms
Part corresponding with the name of the present embodiment haplotype Variant allele is as shown in table 3.
The CYP2D6 allele activity sequencing tables of table 3
| Gene Name | Haplotype | Sequence |
| CYP2D6 | *1 | 4 |
| CYP2D6 | *2 | 3 |
| CYP2D6 | *10 | 2 |
| CYP2D6 | *14 | 1 |
Then, the double type that target gene is obtained according to the name permutation and combination of each haplotype Variant allele becomes
Special-shaped allele names sequence, and double form variation type allele name sequence includes the double form variation of whole of target gene
The name of type allele；And each double form variation type allele is determined according to the enzymatic activity of haplotype Variant allele
Metabolic pattern, and the name of metabolic pattern and corresponding double form variation type allele is associated, obtains a metabolic pattern information table, generation
It is as shown in table 4 to thank to type information table.
The metabolic pattern information table of table 4.
| Gene Name | Diplotype | Metabolic pattern |
| CYP2D6 | *1/*2 | EM |
| CYP2D6 | *1/*10 | EM |
| CYP2D6 | *1/*14 | EM |
| CYP2D6 | *2/*2 | EM |
| CYP2D6 | *2/*10 | EM |
| CYP2D6 | *2/*14 | EM |
| CYP2D6 | *10/*14 | IM |
| CYP2D6 | *10/*10 | EM |
| CYP2D6 | *14/*14 | PM |
Then, the genetic test result that gene sequencing or genechip detection obtain is matched with table 2, obtains everybody
The name of the double form variation type allele of point simultaneously associates the name of double form variation type allele with site, obtains one
The double type name table in site, as shown in table 5.
The double type name table in the site of table 5.
| Gene Name | Detection site | Testing result | Double type |
| CYP2D6 | rs1065852 | GA | *1/*10 |
| CYP2D6 | rs5030865 | TT | *14/*14 |
| CYP2D6 | rs16947 | GG | *1/*1 |
Afterwards, the haplotype variation all according to each site by the name of double form variation type allele in table 5, is extracted
The name of type allele, obtain one first haplotype Variant allele name sequence T, T=[* 1, * 10, * 14, *
14,*1,*1]。
Then, the first haplotype Variant allele is named into sequence T according to table 3, i.e., according to each haplotype anomaly
The enzymatic activity of allele is ranked up from low to high, obtains one second haplotype Variant allele name sequence R, R=
[*14,*14,*10,*1,*1]。
Then, the second haplotype Variant allele name sequence R most the first two haplotype anomaly equipotential is chosen
The name result of one double form variation type allele of unnamed gene composition target gene, the i.e. double form variation type equipotential base
The name result of cause is：(* 14, * 14), this testing result are CYP2D6 (* 14, * 14).
Finally, one is obtained from the metabolic pattern information table search of table 4 according to the name result of double form variation type allele
Metabolic pattern testing result, the metabolic pattern that retrieval obtains this detection CYP2D6 is PM (weak metabolic pattern).
The present invention causes the power of proteinase activity according to different pharmaceutical metabolic enzyme gene SNP site, passes through a set of algorithm
To estimate the life (name of " * " allele) of Variant allele caused by SNP site combination.Due to " * " allele
There is stronger corresponding relation with protein active, can be used directly to judge the metabolic pattern of detection people's drug metabolic enzyme, be that one kind will
The method that drug metabolic enzyme typing gene polymorphisms data are mapped to enzymatic activity metabolism parting.This is instructed according to genetic test
It is significant in terms of personalized medicine.
The present invention is described in detail above in association with accompanying drawing embodiment, those skilled in the art can be according to upper
State and bright many variations example is made to the present invention.Thus, some details in embodiment should not form limitation of the invention, this
Invention will be used as protection scope of the present invention using the scope that appended claims define.
Claims (6)
1. a kind of drug metabolic enzyme metabolic pattern appraisal procedure, including step：
S1：Obtained from a default gene database haplotype Variant allele in the multiple sites of a target gene name and
Gene information, and the gene information will be associated with the name of the corresponding haplotype Variant allele, obtain
One gene information table；
S2：A double type of the target gene is obtained according to the name permutation and combination of each haplotype Variant allele
Variant allele names sequence, and the double form variation type allele name sequence includes the whole of the target gene
The name of double form variation type allele；
S3：The generation of each double form variation type allele is determined according to the enzymatic activity of the haplotype Variant allele
Thank to type, and the metabolic pattern is associated with the name of the corresponding double form variation type allele, obtain a metabolic pattern information
Table；
S4：Obtained according to the genetic test result in the multiple site of the target gene and the gene information table each
The name of the double form variation type allele in the site and by the name of the double form variation type allele with
The site association, obtain the double type name table in a site；
S5：From the site, double type name table extracts the name of all haplotype Variant alleles in each site,
Obtain one first haplotype Variant allele name sequence；
S6：First haplotype is made a variation successively from low to high according to the enzymatic activity of each haplotype Variant allele
The name of each haplotype Variant allele is ranked up in type allele name sequence, obtains one second haplotype
Variant allele names sequence；
S7：Choose most the first two haplotype Variant allele of the second haplotype Variant allele name sequence
Name forms the name result of a double form variation type allele of the target gene；
S8：One metabolism is obtained from the metabolic pattern information table search according to the name result of the double form variation type allele
Type testing result.
2. drug metabolic enzyme metabolic pattern appraisal procedure according to claim 1, it is characterised in that in the S1 steps, institute
Stating gene information includes：Gene Name, with reference to base and mutating alkali yl；The gene information table includes the gene information, position
The name of point information and the haplotype Variant allele.
3. drug metabolic enzyme metabolic pattern appraisal procedure according to claim 2, it is characterised in that the default gene data
Storehouse includes pharmGKB databases and Human cytochrome P450 allele naming committee database.
4. drug metabolic enzyme metabolic pattern appraisal procedure according to claim 3, it is characterised in that in the S3 steps, institute
Stating the metabolic pattern of double form variation type allele includes：Ultra-rapid metabolism type, fast metabolic pattern, intermediate supersession type and weak metabolic pattern.
5. drug metabolic enzyme metabolic pattern appraisal procedure according to claim 4, it is characterised in that in the S4 steps, institute
Stating genetic test result includes the Gene Name, the site information and detection genotype information.
6. drug metabolic enzyme metabolic pattern appraisal procedure according to claim 5, it is characterised in that the genetic test result
Obtained by gene sequencing or genechip detection.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108682458A (en) * | 2018-05-08 | 2018-10-19 | 北京岙特杰诺生物科技有限公司 | Drug use administration method, apparatus and electronic equipment |
| CN112397174A (en) * | 2019-10-31 | 2021-02-23 | 国家卫生健康委科学技术研究所 | Chronic disease medication guidance device and method |
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| CN104212904A (en) * | 2014-09-17 | 2014-12-17 | 武汉康录生物技术有限公司 | Kit for quickly detecting polymorphism of human CYP2C19 gene and using method of kit |
| US20170270246A1 (en) * | 2016-03-21 | 2017-09-21 | Andrius Baskys | Method and system for calculation and graphical presentation of drug-drug or drug-biological process interactions on a smart phone, tablet or computer |
| CN107273710A (en) * | 2017-08-22 | 2017-10-20 | 北京岙特杰诺生物科技有限公司 | A kind of method for the relational model for setting up drug metabolism enzyme gene and drug metabolism |
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2017
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104212904A (en) * | 2014-09-17 | 2014-12-17 | 武汉康录生物技术有限公司 | Kit for quickly detecting polymorphism of human CYP2C19 gene and using method of kit |
| US20170270246A1 (en) * | 2016-03-21 | 2017-09-21 | Andrius Baskys | Method and system for calculation and graphical presentation of drug-drug or drug-biological process interactions on a smart phone, tablet or computer |
| CN107273710A (en) * | 2017-08-22 | 2017-10-20 | 北京岙特杰诺生物科技有限公司 | A kind of method for the relational model for setting up drug metabolism enzyme gene and drug metabolism |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108682458A (en) * | 2018-05-08 | 2018-10-19 | 北京岙特杰诺生物科技有限公司 | Drug use administration method, apparatus and electronic equipment |
| CN112397174A (en) * | 2019-10-31 | 2021-02-23 | 国家卫生健康委科学技术研究所 | Chronic disease medication guidance device and method |
| CN112397174B (en) * | 2019-10-31 | 2021-10-08 | 国家卫生健康委科学技术研究所 | Chronic disease medication guidance device and method |
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