CN103205482A - Plasticizer tracking biomarker, plasticizer tracking genetic chip, and plasticizer tracking biomarker confirmation method - Google Patents
Plasticizer tracking biomarker, plasticizer tracking genetic chip, and plasticizer tracking biomarker confirmation method Download PDFInfo
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- CN103205482A CN103205482A CN2012100074650A CN201210007465A CN103205482A CN 103205482 A CN103205482 A CN 103205482A CN 2012100074650 A CN2012100074650 A CN 2012100074650A CN 201210007465 A CN201210007465 A CN 201210007465A CN 103205482 A CN103205482 A CN 103205482A
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Abstract
The invention discloses a plasticizer tracking biomarker, a plasticizer tracking genetic chip, and a plasticizer tracking biomarker confirmation method. The biomarker found through the confirmation method is one or more of human gene/protein clusters composed of PPARG, CASP3, PPARA, NR1I2, ESR1, AR, CYP1B1, ABCB1, CYP1A1, VEGFA, ESR2, PPARD, LAMP3, BAX, BCL2, CDO1, CELSR2, CSNK1A1, CYP3A4, MAPK1, MAPK3, MYC, NCOA1, PAPSS1, PAPSS2, SUOX, SLC5A5, AKR1C1, IL4, INHA and PCNA, and is suitable for detecting that whether there is pollution of plasticizers, such as phthalate and the like, in a human body or not.
Description
Technical field
The invention relates to a kind of biomarker and confirmation method thereof, particularly about a kind of biomarker and gene chip and confirmation method thereof for the tracking fluidizer.
Background technology
Fluidizer event (be called again the malicious disturbance of fluidizer/mould, fluidizer/mould malicious storm etc.) be Taiwan in a series of food safety events of outburst in by the end of May, 2011.This event rises because the part food inspection goes out to contain fluidizer on the market, and then is found part upstream raw material supplier in common kasher additive " mist generating agent ", uses cheap industrial plasticizing agent with the cost of retrenching.Except initial disclosed beverage product, range of influence also extends to cake, bread and medicine etc.Relevant government bodies are after the event outburst, and bright ordering risen if relevant food is not finished self-checking June in the same year, forbids and peddles.
Make an addition to food product containers such as bottle though fluidizer can be legal, but fluidizer DEHP (phthalic acid two (the 2-ethyl oneself) ester that people's call to attention food and medical container stripping have just been arranged in various countries a long time ago), think that legal denier DEHP just has detrimentally affect.Yet be directly DEHP to be treated as foodstuff additive in this event, content is far above the stripping quantity of past measurement.DEHP is higher 20 times than the toxicity of trimeric cyanamide, not only causes genotoxicity, even carcinogenic danger is arranged.Unworthy dealer adds fluidizer, and health certainly will influence the masses of the people.
Though these fluidizers that are detrimental to health exist the situation in the food to last for a long time, but because the event of all circles does not take place this time to shock, compatriots are to the phychology of ignoring of environmental poisonous substance in addition, to such an extent as to event takes place instantly, none successfully manages stratagem among the people and even government bodies.Radically reform, relevant office more should research and develop relevant poisonous substance screening mode except the chance of the existence that should pay attention to these poisonous substances and education society minimizing use; For the masses that polluted by fluidizer, provide screening and the further measure of protection.Yet these screening modes are still relegated to the category of things wanting at present.
Therefore, the present inventor uses the related background art data, and with minimum cost analysis fluidizer toxicity genome and influence the disease of human body, analysis obtains being suitable for the biomarker of screening fluidizer; (gene chip) is carrier with gene chip, designs the most effective fluidizer screening instrument of minimum cost.The present invention is except the innovation that is association area breaks through, and more human health provides excellent guarantee.
Summary of the invention
The present invention is a kind of for the biomarker of following the trail of fluidizer, is to be selected from the human body gene/protein group that is made up of PPARG, CASP3, PPARA, NR1I2, ESR1, AR, CYP1B1, ABCB1, CYP1A1, VEGFA, ESR2, PPARD, LAMP3, BAX, BCL2, CDO1, CELSR2, CSNK1A1, CYP3A4, MAPK1, MAPK3, MYC, NCOA1, PAPSS1, PAPSS2, SUOX, SLC5A5, AKR1C1, IL4, INHA and PCNA one or more.
According to conception of the present invention, this biomarker can be differentiated human body and whether suffer the fluidizer pollution and cause the gene performance unusual.
According to conception of the present invention, this fluidizer is phthalate (Phthalates).
According to conception of the present invention, this phthalate comprises dioctyl phthalate (DOP) (Diethylhexyl Phthalate, DEHP), phthalic acid two (2-ethylhexyl) ester (Mono-(2-ethylhexyl) Phthalate, MEHP), dibutyl phthalate (Dibutyl Phthalate, DBP), phthalic acid mono (Monobutyl Phthalate, MBP) or the butyl phthalate benzene methyl (Butylbenzyl Phthalate, BBP).
In addition, the present invention has disclosed a kind of for the gene chip of following the trail of fluidizer, and it comprises: human body gene/protein of PPARG, CASP3, PPARA, NR1I2, ESR1, AR, CYP1B1, ABCB1, CYP1A1, VEGFA, ESR2, PPARD, LAMP3, BAX, BCL2, CDO1, CELSR2, CSNK1A1, CYP3A4, MAPK1, MAPK3, MYC, NCOA1, PAPSS1, PAPSS2, SUOX, SLC5A5, AKR1C1, IL4, INHA or PCNA.
The present invention has also disclosed a kind of confirmation method of following the trail of the biomarker of fluidizer, comprises step: selected at least a fluidizer; Define the keyword of this fluidizer, and (Comparative Toxicogenomics Database searches fluidizer-genes matter interactions that all are correlated with in CTD) in poison genes group database relatively with this keyword; Selected interaction result from the human body genes matter; Confirm the molecular function (Molecular Function) of this fluidizer-genes matter; And if this molecular function and a human lesion have a significant probability that takes place, then confirm to cause the genes matter of this molecular function for following the trail of the biomarker of this fluidizer.
According to conception of the present invention, this human lesion comprises: cardiac failure (Heart Failure), tachycardia (Tachycardia), myocardial infarction (Cardiac Infarction), stagnation of the blood heart failure (Congestive Cardiac Failure), Arrhythmias (Cardiac Arrhythmia), hepatic necrosis (Liver Necrosis/Cell Death), fatty liver (Liver Steatosis), hepatomegaly (Liver Hepatomegaly), hepatitis (Liver Hepatitis), liver hyperplasia (Liver Hyperplasia/Hyperproliferation), renal failure (Kidney Failure), ephritis (Renal Nephritis), renal hypertrophy (Renal Proliferation), uronephrosis (Renal Hydronephrosis) or renal necrosis (Renal Necrosis/Cell Death).
According to conception of the present invention, this generation probability p value is less than 0.05.
Description of drawings
Fig. 1 is the schema of the embodiment of the invention.
Embodiment
Before beginning to describe embodiments of the invention, do detailed explanation with regard to background information of the present invention earlier.The present invention utilizes existing gene database, and in a particular manner, screening goes out suitable biomarker (gene or protein), and be probe, make suitable gene chip.
General is carried out the detection of fluidizer content at food, article or blood at present, but can't know why whether fluidizer have influence on human body or effect really, therefore, the present invention is from the gene of human body 2～30,000, find out the oligogene group that influenced by fluidizer, that is to say, can change its expression amount because of fluidizer, by this, as biomarker or gene chip.
The employed gene database of present embodiment for poison genes group database relatively (Comparative Toxicogenomics Database, CTD).This database is a public web site, and the research tool of the science data, gene and the human diseases that concern between the chemical is described in planning.One of major objective of CTD is that the pushing ring environmental chemicals is to the understanding of the influence of human health.Because the composition of its content is complete real-time experimental data, scientific report and paper analysis, effectively analyzes this database and can save unnecessary time and money expense, obtains the information of most complete poisonous substance and environment and disease simultaneously.
Gene chip is the specific glass sheet or the silicon crystal unit sheet that have dna microarray (micorarray), lays thousands of or tens thousand of nucleic acid probes at several square centimeters areas; DNA in the corpse or other object for laboratory examination and chemical testing, cDNA, RNA etc. detect by modes such as fluorescence or electric currents after probe is combined.Via once test, can provide a large amount of gene order relevant informations.It is the instrument of genomics and genetics research.The genetic expression of the analysis a large amount of (thousands of) that researchist's applying gene chip is just can be at one time quantitative, have fast, accurately, bioanalysis detectability cheaply.In conjunction with above-mentioned analysis biomarker later, be core of the present invention.
Embodiments of the invention are asked for an interview Fig. 1 with flow chart description shown in Figure 1.According to spirit of the present invention, a kind of biomarker confirmation method of following the trail of fluidizer, at first selected at least a fluidizer (step S1).Selected person is phthalate (Phthalates) herein.Quite a lot of based on the phthalic acid salt that daily life often runs into, selected two the dioctyl phthalate (DOP) of normal chance (Diethylhexyl Phthalate, DEHP) and dibutyl phthalate (Dibutyl Phthalate DBP) searches analysis.Further can produce metabolite in vivo because of this two, for having avoided leakage, together with its metabolite phthalic acid two (2-ethylhexyl) ester (Mono-(2-ethylhexyl) Phthalate, MEHP), phthalic acid mono (Monobutyl Phthalate, MBP) and the butyl phthalate benzene methyl (Butylbenzyl Phthalate BBP) searches in the lump.
Next defines the keyword of aforementioned fluidizer, and (Comparative Toxicogenomics Database searches fluidizer-genes matter interactions (step S2) that all are correlated with in CTD) in poison genes group database relatively with this keyword.This keyword adds to abridge with its formal name used at school and carries out database search.Selected interaction result from the human body genes matter (step S3).Find that by analytical results DEHP/MEHP has 183 relevant genes matter, DBP/MBP/BBP has 112 relevant genes matter.Remove the genes matter of both double countings, add up to 249 different genes matter.
Again, confirm the molecular function (Molecular Function) (step S4) of aforementioned genes matter.Except traditional read data storehouse content confirming this molecular function because all digitizings of data of database, common software, as MetaCore or Pathway Studio etc., all can be in order to assist look for the molecular function of these 249 genes matter.
At last, determine the biomarker of aforementioned tracking fluidizer (DEHP/MEHP and DBP/MBP/BBP).If this molecular function and human lesion have non-vanishing generation probability, confirm then to cause that the genes matter of this molecular function is for following the trail of the biomarker (step S5) of this fluidizer.Human lesion described herein is cardiac failure (Heart Failure), tachycardia (Tachycardia), myocardial infarction (Cardiac Infarction), stagnation of the blood heart failure (Congestive Cardiac Failure), Arrhythmias (Cardiac Arrhythmia, hepatic necrosis (Liver Necrosis/Cell Death), fatty liver (Liver Steatosis), hepatomegaly (Liver Hepatomegaly), hepatitis (Liver Hepatitis), liver hyperplasia (Liver Hyperplasia/Hyperproliferation), renal failure (Kidney Failure), ephritis (Renal Nephritis), renal hypertrophy (Renal Proliferation), uronephrosis (Renal Hydronephrosis) or renal necrosis (Renal Necrosis/Cell Death).It is less than 0.05 because there is the probability p value that takes place in aforementioned fluidizer.
By analysis, the genes matter that influenced by fluidizer DEHP/MEHP has 26 groups: PPARG, CASP3, PPARA, NR1I2, ESR1, AR, CYP1B1, ABCB1, CYP1A1, VEGFA, ESR2, PPARD, LAMP3, BAX, BCL2, CDO1, CELSR2, CSNK1A1, CYP3A4, MAPK1, MAPK3, MYC, NCOA1, PAPSS1, PAPSS2 and SUOX.
And the genes matter that influenced by fluidizer DBP/MBP/BBP has 15 groups: PPARG, PPARA, NR1I2, ESR1, AR, CYP1B1, VEGFA, ESR2, PPARD, LAMP3, SLC5A5, AKR1C1, IL4, INHA and PCNA.
Comprehensive above the analysis, can learn and influenced by fluidizer DEHP/MEHP and DBP/MBP/BBP and the genes matter of corresponding above-mentioned human lesion has 31 groups: PPARG, CASP3, PPARA, NR1I2, ESR1, AR, CYP1B1, ABCB1, CYP1A1, VEGFA, ESR2, PPARD, LAMP3, BAX, BCL2, CDO1, CELSR2, CSNK1A1, CYP3A4, MAPK1, MAPK3, MYC, NCOA1, PAPSS1, PAPSS2, SUOX, SLC5A5, AKR1C1, IL4, INHA, and PCNA, it is the biomarker that the present invention is used for following the trail of fluidizer (DEHP/MEHP and DBP/MBP/BBP).
That is to say, when above-mentioned listed genomic expression amount differs from normal value, can judge that then the testee is subjected to the fluidizer effect to be higher than normal standard range.Therefore, can from said gene/protein group, select partly or entirely as biomarker to differentiate human body and polluted by fluidizer and to cause abnormal gene expression.More particularly, if want human body polluted by fluidizer DBP/MBP/BBP and cause abnormal gene expression, in fact, be not limited to and all detect at above-mentioned 15 groups of listed genes matter, and only need select wherein several groups.
According to spirit of the present invention, comprise aforesaid gene or protein group and be used for the biochip that detecting fluidizer (DEHP/MEHP and DBP/MBP/BBP) influences, also in the present patent application protection domain.
Though the present invention discloses as above with embodiment; so it is not in order to limit the present invention; those skilled in the art without departing from the spirit and scope of the present invention; when doing a little change and retouching; but all will fall within the scope of protection of the present invention, protection scope of the present invention should be as the criterion with claims scope required for protection.
Claims (8)
1. biomarker of be used for following the trail of fluidizer is to be selected from the human body gene/protein group that is made up of PPARG, CASP3, PPARA, NR1I2, ESR1, AR, CYP1B1, ABCB1, CYP1A1, VEGFA, ESR2, PPARD, LAMP3, BAX, BCL2, CDO1, CELSR2, CSNK1A1, CYP3A4, MAPK1, MAPK3, MYC, NCOA1, PAPSS 1, PAPSS2, SUOX, SLC5A5, AKR1C1, IL4, INHA and PCNA one or more.
2. as claimed in claim 1 for the biomarker of following the trail of fluidizer, wherein whether this biomarker suffers the fluidizer pollution and causes abnormal gene expression in order to differentiate human body.
3. as claimed in claim 1 for the biomarker of following the trail of fluidizer, wherein this fluidizer is phthalate (Phthalates).
4. as claimed in claim 3 for the biomarker of following the trail of fluidizer, wherein this phthalate comprises dioctyl phthalate (DOP) (Diethylhexyl Phthalate, DEHP), phthalic acid two (2-ethylhexyl) ester (Mono-(2-ethylhexyl) Phthalate, MEHP), dibutyl phthalate (Dibutyl Phthalate, DBP), phthalic acid mono (Monobutyl Phthalate, MBP) or the butyl phthalate benzene methyl (Butylbenzyl Phthalate, BBP).
5. a gene chip that is used for following the trail of fluidizer comprises: human body gene/protein of PPARG, CASP3, PPARA, NR1I2, ESR1, AR, CYP1B1, ABCB1, CYP1A1, VEGFA, ESR2, PPARD, LAMP3, BAX, BCL2, CDO1, CELSR2, CSNK1A1, CYP3A4, MAPK1, MAPK3, MYC, NCOA1, PAPSS1, PAPSS2, SUOX, SLC5A5, AKR1C1, IL4, INHA or PCNA.
6. biomarker confirmation method of following the trail of fluidizer comprises step:
(1) selected at least a fluidizer;
(2) define the keyword of this fluidizer, and (Comparative Toxicogenomics Database searches fluidizer-genes matter interactions that all are correlated with in CTD) in poison genes group database relatively with this keyword;
(3) selected interaction results from the genes matter in the human body;
(4) confirm the molecular function of this fluidizer-genes matter; And
(5) if this molecular function and human lesion have non-vanishing generation probability, then confirm to cause the genes matter of this molecular function for following the trail of the biomarker of this fluidizer.
7. the biomarker confirmation method of tracking fluidizer as claimed in claim 6, wherein this human lesion comprises: cardiac failure (Heart Failure), tachycardia (Tachycardia), myocardial infarction (Cardiac Infarction), stagnation of the blood heart failure (Congestive Cardiac Failure), Arrhythmias (Cardiac Arrhythmia), hepatic necrosis (Liver Necrosis/Cell Death), fatty liver (Liver Steatosis), hepatomegaly (Liver Hepatomegaly), hepatitis (Liver Hepatitis), liver hyperplasia (Liver Hyperplasia/Hyperproliferation), renal failure (Kidney Failure), ephritis (Renal Nephritis), renal hypertrophy (Renal Proliferation), uronephrosis (Renal Hydronephrosis) or renal necrosis (Renal Necrosis/Cell Death).
8. the biomarker confirmation method of tracking fluidizer as claimed in claim 6, wherein this generation probability p value is less than 0.05.
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| CN105040109A (en) * | 2015-05-28 | 2015-11-11 | 宁波大学 | Gene chip for detecting environmental pollutant DEHP (di-2-ethylhexyl phthalate), and preparation method and application thereof |
| WO2017024682A1 (en) * | 2015-08-12 | 2017-02-16 | 快克生物有限责任公司 | Method for preparing function verification chip of biomarker |
| CN113973772A (en) * | 2021-10-22 | 2022-01-28 | 中国水产科学研究院珠江水产研究所 | Application of passive integrated transceiver chip in soft-shelled turtle individual tracking monitoring |
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Application publication date: 20130717 |