CN107502667A - Related gene function hereditary variation horizontal to LDL C and related application - Google Patents
Related gene function hereditary variation horizontal to LDL C and related application Download PDFInfo
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Abstract
The invention provides related gene function hereditary variation horizontal to LDL C and related application；Specifically, the invention provides the reagent material and/or instrument and equipment of following Argine Monohydrochloride site and/or its corresponding gene loci in sample of the detection from test individual to prepare the application in being used to assess the detecting system of blood lipid level, dyslipidemia and/or incidence of coronary heart disease risk：EV15 gene rs117711462, APOB gene rs376825639 and/or PKD1L3 genes rs17358402 causes the amino acids of EVI5 albumen the 354th, the amino acids of APOB albumen the 3768th and/or the amino acids of PKD1L3 albumen the 1572nd coding to change respectively.The test individual for EVI5Arg354Cys and/or PKD1L3Arg1572His variations occur has higher T-CHOL and/or low-density lipoprotein cholesterol level and/or higher dyslipidemia onset risk.The test individual for APOBIle3768Thr variations occur has relatively low low-density lipoprotein cholesterol level, relatively low dyslipidemia onset risk and/or relatively low incidence of coronary heart disease risk.
Description
Technical field
The present invention is on related gene function hereditary variation horizontal to LDL-C and related application, specifically, sheet
Invention be on detection the sample from test individual in EVI5Arg354Cys, APOBIle3768Thr,
The reagent material and/or instrument and equipment of PKD1L3Arg1572His variation situation are being prepared for assessing blood lipid level, blood fat
Application in the detecting system of exception and/or incidence of coronary heart disease risk, further relate to it is a kind of assess blood lipid level, dyslipidemia and/
Or the detecting system of incidence of coronary heart disease risk.
Background technology
Numerous studies data shows that dyslipidemia is coronary heart disease, myocardial infarction, sudden cardiac death and cerebral arterial thrombosis
Independent hazard factor.It causes concealment, gradual, progressive, systemic and device to body by accelerating systemic atherosclerosis
The infringement of matter.Studies have shown that crowd's blood cholesterol levels often raise 1%, coronary heart disease (CAD) morbidity increase by 2%~3%.I
It is in notable trend, 2007~2008 years China national diabetes and metabolic disorder result of study that state's patients with dyslipidemia sum, which rises,
Prompting, more than the 20 years old crowd's cholesterol levels in China added 23.9% compared with 2002, and dyslipidemia has become China
The important public hygiene problem of resident.2011 annual Beijing's health show that Beijing is normal with population health status report data
Super half citizen dyslipidemia in the people is lived, wherein the dyslipidemia illness rate of 18~30 years old male has reached 58.5%.
Total plasma cholesterol (TC), LDL-C (LDL-C), HDL-C (HDL-C)
It is the target spot and target of the most important hazards of angiocardiopathy and Results with triglycerides (TG) concentration.World health
Organize in update prompting angiocardiopathy prevention and control benefit, contribution caused by the control of dyslipidemia hazards is maximum.It is beautiful
State's coronary heart disease death drop by half during 1980~2000 years, the tribute carried out made by national cholesterol education is attributed to the fact that completely
Offer.
Most of dyslipidemias have complicated Etiologic Mechanism, be between multiple genes or multiple genes with environment because for a long time
The result of interaction.Genome-wide association study has been successfully determined multiple genetic locuses related to blood fat, however, almost
All these sites are determined in the crowd of European descent, lack the data in asian population.In addition,
The functional site in major gene region is often rare low frequency site, has important functional meaning and clinical meaning, result of study
Show that there is kind of a group specificity for the rare variation (80%) of most functions.In view of the environment between asian population and European
The difference of exposure and genetic background is huge, therefore it is related to need system examination blood fat in identification asian population particularly Chinese population badly
Function variation and rare variation, it will help to the prevention of compatriots' hyperlipidemia, new drug development, diagnosis and individualized treatment.
The content of the invention
It is a primary object of the present invention to determine the related to blood lipid level of asian population particularly gook's group specificity
Gene function hereditary variation, there is provided assess blood lipid level and/or dyslipidemia by detecting correlated inheritance site and fall ill wind
The method of danger, and the detecting system and related application for assessing blood lipid level and/or dyslipidemia onset risk are provided.
Inventor includes Chinese, Filipino, Chinese American, the Singapore nationality foreign citizen of Chinese origin, Singapore with East Asia crowd
Nationality Malaysian etc. is research object, the incidence relation of individual hereditary variation and blood lipid level more than 110,000 of having analyzed and researched, it is determined that
To T-CHOL (TC) and/or the horizontal related gene function hereditary variation of LDL-C (LDL-C).Institute
The gene function hereditary variation stated includes following Argine Monohydrochloride site and/or the variation of its corresponding gene loci：EVI5
The amino acids of albumen the 354th, the amino acids of APOB albumen the 3768th and/or the amino acids of PKD1L3 albumen the 1572nd.Wherein, egg
Gene loci corresponding to casamino acid site refers to correspond to the amino acid in the nucleotide sequence of the gene of encoding said proteins
The nucleotide site in site.Preferably, gene loci corresponding to the amino acids of EVI5 albumen the 354th includes EVI5 genes
rs117711462；Gene loci corresponding to the amino acids of APOB albumen the 3768th includes APOB genes rs376825639；
Gene loci corresponding to the amino acids of PKD1L3 albumen the 1572nd includes PKD1L3 genes rs17358402.
In the present invention, term " EVI5 " includes EVI5 genes and/or EVI5 albumen；Term " APOB " includes APOB genes
And/or APOB albumen；Term " PKD1L3 " includes PKD1L3 genes and/or PKD1L3 albumen.
The research of the present invention shows that the amino acids of EVI5 albumen the 354th are Cys (for example, EVI5 genes
Rs117711462 be A situation) test individual there is higher T-CHOL and/or low-density lipoprotein cholesterol level
And/or higher dyslipidemia onset risk；The amino acids of APOB albumen the 3768th are Thr (for example, APOB genes
Rs376825639 is G situation) test individual have relatively low T-CHOL and/or low-density lipoprotein cholesterol level,
Relatively low dyslipidemia onset risk and/or relatively low incidence of coronary heart disease risk；The amino acids of PKD1L3 albumen the 1572nd are His
The test individual of (for example, PKD1L3 genes rs17358402 is T situation) has higher T-CHOL and/or low density lipoprotein
The horizontal and/or higher dyslipidemia onset risk of protein cholesterol.
So as to by detecting in the sample from test individual with the presence or absence of the Argine Monohydrochloride site and/or its is right
The variation situation for the gene loci answered, it can be used for assessing test individual blood lipid level particularly T-CHOL (TC) and/or low
Density lipoprotein-cholesterol (LDL-C) is horizontal, may also be used for assessing test individual dyslipidemia and/or incidence of coronary heart disease wind
Danger.
On the one hand, the invention provides detection the sample from test individual in following Argine Monohydrochloride site and/or its
The reagent material and/or instrument and equipment of corresponding gene loci are being prepared for assessing blood lipid level, dyslipidemia and/or coronary disease
Application in the detecting system of sick onset risk：
The 1572nd amino acids of EVI5 albumen the 354th, the amino acids of APOB albumen the 3768th and/or PKD1L3 albumen ammonia
Base acid；
Wherein, gene loci corresponding to Argine Monohydrochloride site refers in the nucleotide sequence of the gene of encoding said proteins
The nucleotide site of the corresponding amino acid sites；Preferably, the corresponding gene loci is EVI5 genes
Rs117711462, APOB gene rs376825639 and/or PKD1L3 gene rs17358402.
According to specific embodiments of the present invention, in of the invention, blood lipid level includes T-CHOL (TC) and/or low-density
Lipoprotein cholesterol (LDL-C).
According to specific embodiments of the present invention, in of the invention, the amino acids of EVI5 albumen the 354th are Cys or EVI5 bases
Carrier (rs117711462 A, amino acid are changed into Cys) body that the rs117711462 allele of cause is A has higher
T-CHOL and/or low-density lipoprotein cholesterol level and/or higher dyslipidemia onset risk.
According to specific embodiments of the present invention, in of the invention, the amino acids of APOB albumen the 3768th are Thr or APOB bases
Because the carrier (rs376825639 G, amino acid are changed into Thr) that rs376825639 allele is G has relatively low total courage
Sterol and/or low-density lipoprotein cholesterol level, relatively low dyslipidemia onset risk and/or relatively low incidence of coronary heart disease wind
Danger.
According to specific embodiments of the present invention, in the present invention, the amino acids of PKD1L3 albumen the 1572nd be His or
The carrier (rs17358402 T, amino acid are changed into His) that PKD1L3 gene rs17358402 allele is T has higher
T-CHOL and/or low-density lipoprotein cholesterol level and/or higher dyslipidemia onset risk.
According to specific embodiments of the present invention, in the present invention, the test individual is East Asia crowd, including Chinese,
Filipino, Chinese American, the Singapore nationality foreign citizen of Chinese origin, Singapore nationality Malaysian etc..During specific detection, the sample may be from
Blood, urine, saliva, gastric juice, hair or biopsy of test individual etc., preferably blood.
Possible technique any in this area can be used to detect Argine Monohydrochloride site of the present invention in protein level,
It can also detect corresponding to Argine Monohydrochloride site of the present invention that (example is as the aforementioned for gene loci in DNA level, rna level
Mononucleotide polymorphism site) to detect gene function hereditary variation situation.Protein level detection method for example：Egg
The gene sequence analysis of white matter and peptide fragment, including the chemical method Edman methods of N-terminal sequencing, C-terminal enzyme solution, C end
Hold chemical degradation method etc.；The protein detection techniques related to mass spectrum, such as substance assistant laser desorpted ionized/flight time mass spectrum
Mensuration (MALDI-TOF MS) and electronic spraying MALDI-MS mensuration (electrosprayion-
izationmassspectrometry,ESI-MS)；Detection method based on antibody, such as prepare recognizable different mutants
Antibody, protein variant is detected using Western blotting (such as western blot) and/or Enzyme-linked Immunosorbent Assay (ELISA).In DNA water
Flat, rna level detection method is for example：The method that direct Sequencing can be used, can directly be disclosed pair by DNA direct Sequencings
According to gene and the sequence difference between mutator is carried, can be specifically traditional use business sequencing kit or automatic survey
DNA is directly sequenced sequence instrument, or develop in recent years pyrosequencing (Pyrosequencing), micro sequence
(SNaPshot) etc..The method based on hybridization can also be used, specifically includes Taqman sonde methods, DNA chip method etc..Can be with
Using the method based on primer extend, such as Matrix Assisted Laser Desorption ion flight time mass spectrum (MALDI-Tof-MS).May be used also
With use the method based on conformation, specifically for example RFLP (RFLP) analysis, single-strand conformation polymorphism
(single-strand conformational polymorphism, SSCP) analysis, denaturing gradient gel electrophoresis
(denaturing gradient gel electrophoresis, DGGE) analysis, Denaturing high performance liquid chromatography
Analytical technologies such as (denaturing high performance liquid chromatography, dHPLC).It can also adopt
With high-resolution solubility curve analytical technology (HRM).In the specific implementation, those skilled in the art can be according to actual conditions
Select above-mentioned any technology vitro detection Argine Monohydrochloride site of the present invention and/or gene loci (including the list
Nucleotide polymorphic site), can also be using the combination of multiple technologies come vitro detection.
It is described to detect the Argine Monohydrochloride site and/or gene in of the invention according to specific embodiments of the present invention
The reagent material and/or instrument and equipment in site can be any feasible detection Argine Monohydrochloride site and/or gene position
Used reagent material and/or instrument and equipment etc. in the technology of point.It is included in the 386th, protein level detection CD36 albumen
The reagent material of amino acid, the amino acids of APOA1 albumen the 61st and/or the amino acids of CETP albumen the 74th；And/or in DNA water
Flat, rna level detection CD36 gene rs148910227, APOA1 gene rs12718465 and/or CETP genes rs201790757
Reagent material.In the reagent material that protein level detects for example：Examination for the gene sequence analysis of protein and peptide section
Agent material；Or the reagent material for the protein detection techniques related to mass spectrum；Or for the detection method based on antibody
Reagent material etc..In the reagent material that DNA level, rna level detect for example：Reagent for direct sequencing；Or for gathering
The reagent that polymerase chain reaction is combined with restriction fragment length polymorphism analysis；Or for PCR and directly
The reagent that PCR sequencing PCR is combined；Or the reagent being combined for PCR with direct sequencing；Or for following
A kind of reagent of SNP classifying methods：Method based on hybridization, the method based on primer extend, the method based on conformation or high score
Resolution solubility curve analytical technology etc..
On the other hand, present invention also offers a kind of assessment blood lipid level, dyslipidemia and/or incidence of coronary heart disease risk
Detecting system, it includes：Detect following Argine Monohydrochloride site and/or its corresponding gene position in the sample from test individual
The reagent material and/or instrument and equipment of point：
The 1572nd amino acids of EVI5 albumen the 354th, the amino acids of APOB albumen the 3768th and/or PKD1L3 albumen ammonia
Base acid；
Wherein, gene loci corresponding to Argine Monohydrochloride site refers in the nucleotide sequence of the gene of encoding said proteins
The nucleotide site of the corresponding amino acid sites；Preferably, the corresponding gene loci is EVI5 genes
Rs117711462, APOB gene rs376825639 and/or PKD1L3 gene rs17358402.
According to specific embodiments of the present invention, assessment blood lipid level, dyslipidemia and/or incidence of coronary heart disease of the invention
The detecting system of risk, it includes detection unit and assessment unit, wherein：
The detection unit includes Argine Monohydrochloride site described in sample of the detection from test individual and/or it is corresponding
Gene loci reagent material and/or instrument and equipment, for obtaining test individual albumen and/or gene function hereditary variation
The testing result of situation；
The assessment unit includes being used for the processing unit for according to the testing result of detection unit assess processing；Its
In, the amino acids of EVI5 albumen the 354th be the rs117711462 allele of Cys or EVI5 genes be A carrier have compared with
High T-CHOL and/or low-density lipoprotein cholesterol level and/or higher dyslipidemia onset risk；APOB albumen
3768 amino acids are that the carrier that Thr or APOB gene rs376825639 allele is G has relatively low T-CHOL
And/or low-density lipoprotein cholesterol level and/or relatively low dyslipidemia onset risk；The bit amino of PKD1L3 albumen the 1572nd
Acid is that the carrier that His or PKD1L3 gene rs17358402 allele is T has higher T-CHOL and/or low-density
Lipoprotein cholesterol level and/or higher dyslipidemia onset risk.
The detecting system for assessing blood lipid level, dyslipidemia and/or incidence of coronary heart disease risk of the present invention, can be virtual
Device, as long as the function of the detection unit and assessment unit can be realized.Described detection unit can be included respectively
Kind detection reagent material and/or detecting instrument equipment etc.；Described data analysis unit can be any can realize to detection
The testing result of unit is analyzed and processed and draws blood lipid level, dyslipidemia and/or incidence of coronary heart disease risk assessment situation
Computing instrument, module or virtual unit, such as can be in advance by various possible testing results and corresponding blood fat water
Flat (including LDL-C is horizontal), dyslipidemia and/or incidence of coronary heart disease risk formulate corresponding data drawing list, by detection unit
Testing result, which compares the data drawing list, can draw blood lipid level, dyslipidemia and/or incidence of coronary heart disease risk evaluation result.
Using the technology of the present invention, East Asia crowd's blood fat can be assessed by detecting the gene function hereditary variation
Horizontal and/or dyslipidemia onset risk, makes the individuation health action scheme for research object, and will be helpful to pair
The prevention of compatriots' hyperlipidemia, new drug development, diagnosis and individualized treatment.
Embodiment
In order to be more clearly understood that the present invention, the present invention is further described referring now to the following example.Embodiment is only used for
Explain without limiting the invention in any way.The experimental method of unreceipted actual conditions is known to art in embodiment
Conventional method and normal condition, or according to the condition proposed by manufacturer.
Embodiment one
Research detects and analyzed respectively the hereditary variation dependency relation related to LDL-C LDL-C.It is first
First, to the carry out Exon chip detection of 23 47532 research objects studied of East Asia crowd.Research sample comes from Chinese eye
Section's research (CHES), China's Healthy and nutrition survey (CHNS), Port of Fangcheng men's health inspection investigation (FAMHES), Guizhou Bijie
Diabetes B research (GBTDS), Hong Kong University's special item plan (HKU-TRS), Hubei coronary heart disease research (HuCAD) and in
23 researchs such as state's aged's nutrition and investigation of health conditions (NHAPC).It is outer used in 23 independent blood lipid level researchs
Situations such as showing sub- chip detection platform, genotype-phenotype analysis software is shown in Table 1.Merge all samples and be associated analysis, exclude
Association analysis is included in final 110986 hereditary variation in singlet site, and the significance,statistical of research is set to P<4.5×10-7。
The Exon chip detection technique platform and analysis software of 1 23 research samples of table
Not no while influence coronary heart disease CAD risks in order to further assess the notable site of blood fat, we apply gook
Group's CAD data has carried out case-control study, and the data include Peking University's health science center and medical college of University of Michigan
The research (PUUMA-MI) of myocardial infarction, Hong Kong University's special item plan (HKU-TRS), Hubei coronary heart disease research (HuCAD),
Beijing atherosclerosis study (BAS) and Chinese atherosclerosis study (CAS), wherein have 9661 CAD patients and
18558 controls, 28899 altogether.
Statistical analysis technique
When meta is analyzed, LDL-C indexs measured in each queue are respectively studied by age, age quadratic sum
It is the standardized normal distribution that 0 standard deviation is 1 that specific covariant, which is adjusted and is converted into average,.Use
RAREMETALWORKER or RVTESTS softwares associate pass with HDL-C to analyzing hereditary variation in each research sample respectively
System, and then use the result of each research of RAREMETALS softwares progress meta analysis merging.Study and use with CAD risks
Case-control designs, and analyzes the notable site of blood fat and CAD relation in each research, and application METAL fixed effect is reciprocal
Weight meta analyses and merge each result of study.
The basic condition of study population
Meta analyses include East Asia crowd's sample of 23 research, and 47532 research objects, grind from Chinese ophthalmology altogether
Study carefully (CHES), China's Healthy and nutrition survey (CHNS), Port of Fangcheng men's health inspection investigation (FAMHES), the type of Guizhou Bijie 2
Diabetes study (GBTDS), Hong Kong University's special item plan (HKU-TRS), Hubei coronary heart disease research (HuCAD), China are old
23 researchs such as age population nutrition and investigation of health conditions (NHAPC), sample essential characteristic such as table 2 below.Coronary heart disease CAD association
Research includes 9661 CAD patients and 18558 controls, from Peking University's health science center and medical college of University of Michigan
The research (PUUMA-MI) of myocardial infarction, Hong Kong University's special item plan (HKU-TRS), Hubei coronary heart disease research (HuCAD),
Beijing atherosclerosis study (BAS) and Chinese atherosclerosis study (CAS).Each research obtain its research institution and
Local fact-finding organ Ethics Committee approval.The written signature informed consent form of all participants.
The Exon chip of table 2 detects crowd's essential information
Abbreviation：CHES, Chinese ophthalmology research；CHNS, China's Healthy and nutrition survey；CLHNS, cebu longitudinal direction health and battalion
Support investigation；FAMHES, Port of Fangcheng men's health inspection investigation；GBTDS：Guizhou Bijie diabetes B research；HKU-TRS, Hong Kong
University's special item plan；HuCAD, Hubei coronary heart disease research；NHAPC, Chinese aged's nutrition and investigation of health conditions；
PUUMA, the research of Peking University's health science center and medical college of University of Michigan myocardial infarction；SBCS, Shanghai breast cancer are ground
Study carefully；SCES, the research of Chinese eye section of Singapore；SiMES, Singapore's Malaysian's ophthalmology research；SMHS, Shanghai men's health are ground
Study carefully；SP2, Singapore's perspective study project；SWHS, Shanghai women's health research；TUDR, U.S.'s Taiwanese's diabetic retina
Disease research；TC, T-CHOL；LDL-C, LDL-C；HDL-C, HDL-C；TG, glycerine
Three fat；BMI, body mass index.
Table 3 lists meta analyses EVI5Arg354Cys, and (EV15 genes rs117711462 is A, the 354th, EVI5 albumen
Amino acid sports Cys by Arg), (APOB genes rs376825639 is G to APOBIle3768Thr, the 3768th, APOB albumen
Amino acid sports Thr by Ile), (PKD1L3 genes rs17358402 is T to PKD1L3Arg1572His, PKD1L3 albumen
1572 amino acids sport His by Arg) and LDL-C association results.Table 4 be APOBIle3768Thr with
CAD association results.
Table 3 EVI5Arg354Cys, APOBIle3768Thr, PKD1L3Arg1572His and LDL-C
Association results
The APOB genes Ile3768Thr of table 4 and CAD association results
The analyze data of the present invention shows that EVI5Arg354Cys, APOBIle3768Thr and PKD1L3Arg1572His are equal
It is significantly correlated with LDL-C, reach significance (the P values respectively 3.23 × 10 of research-7、3.35×10-9With 2.11 × 10-8), research of the invention also shows these three sites of EVI5Arg354Cys, APOBIle3768Thr and PKD1L3Arg1572His
Also up to the significance of research, (P values are respectively 1.41 × 10 with TC levels-7、8.44×10-12With 1.96 × 10-9).Simultaneously
APOBIle3768Thr is also significantly correlated with coronary heart disease, G allele (3768 amino acids sport Thr) carrier have compared with
The horizontal risks that coronary heart disease occurs simultaneously of low LDL-C reduce by 80% (OR=0.19,95%CI=-0.51-0.88, P=2.06
×10-6)。
Claims (10)
1. detect the reagent material of following Argine Monohydrochloride site and/or its corresponding gene loci in the sample from test individual
Material and/or instrument and equipment are being prepared for assessing in the detecting system of blood lipid level, dyslipidemia and/or incidence of coronary heart disease risk
Application：
The amino acids of EVI5 albumen the 354th, the amino acids of APOB albumen the 3768th and/or the bit amino of PKD1L3 albumen the 1572nd
Acid；
Wherein, gene loci corresponding to Argine Monohydrochloride site refers to correspond in the nucleotide sequence of the gene of encoding said proteins
The nucleotide site of the amino acid sites；Preferably, gene loci corresponding to described for EVI5 genes rs117711462,
APOB gene rs376825639 and/or PKD1L3 genes rs17358402.
2. application according to claim 1, wherein, blood lipid level includes T-CHOL (TC) and/or low-density lipoprotein
Cholesterol (LDL-C) is horizontal.
3. application according to claim 1, wherein, the amino acids of EVI5 albumen the 354th are Cys or EVI5 genes
Rs117711462 allele is that A carrier has higher T-CHOL and/or low-density lipoprotein cholesterol level
And/or higher dyslipidemia onset risk.
4. application according to claim 1, wherein, the amino acids of APOB albumen the 3768th are Thr or APOB genes
The carrier that rs376825639 allele is G have relatively low T-CHOL and/or low-density lipoprotein cholesterol level,
Relatively low dyslipidemia onset risk and/or relatively low incidence of coronary heart disease risk.
5. application according to claim 1, wherein, the amino acids of PKD1L3 albumen the 1572nd are His or PKD1L3 genes
Rs17358402 allele be T carrier have higher T-CHOL and/or low-density lipoprotein cholesterol level and/
Or higher dyslipidemia onset risk.
6. application according to claim 1, wherein, the test individual is East Asia crowd.
7. application according to claim 1, wherein, blood of the sample from test individual, urine, saliva, gastric juice, head
Hair or biopsy, preferably blood.
8. a kind of detecting system for assessing blood lipid level, dyslipidemia and/or incidence of coronary heart disease risk, it includes：Detection comes from
The reagent material and/or instrument of following Argine Monohydrochloride site and/or its corresponding gene loci are set in the sample of test individual
It is standby：
The amino acids of EVI5 albumen the 354th, the amino acids of APOB albumen the 3768th and/or the bit amino of PKD1L3 albumen the 1572nd
Acid；
Wherein, gene loci corresponding to Argine Monohydrochloride site refers to correspond in the nucleotide sequence of the gene of encoding said proteins
The nucleotide site of the amino acid sites；Preferably, gene loci corresponding to described for EVI5 genes rs117711462,
APOB gene rs376825639 and/or PKD1L3 genes rs17358402.
9. detecting system according to claim 8, it includes detection unit and assessment unit, wherein：
The detection unit includes Argine Monohydrochloride site and/or its corresponding base described in sample of the detection from test individual
Because of the reagent material and/or instrument and equipment in site, for obtaining the detection knot of test individual gene function hereditary variation situation
Fruit；
The assessment unit includes being used for the processing unit for according to the testing result of detection unit assess processing；Wherein,
The amino acids of EVI5 albumen the 354th be the rs117711462 allele of Cys or EVI5 genes be A carrier have it is higher
T-CHOL and/or low-density lipoprotein cholesterol level and/or higher dyslipidemia onset risk；APOB albumen
3768 amino acids are that the carrier that Thr or APOB gene rs376825639 allele is G has relatively low T-CHOL
And/or low-density lipoprotein cholesterol level, relatively low dyslipidemia onset risk and/or relatively low incidence of coronary heart disease risk；
The amino acids of PKD1L3 albumen the 1572nd be His or PKD1L3 gene rs17358402 allele be T carrier have compared with
High T-CHOL and/or low-density lipoprotein cholesterol level and/or higher dyslipidemia onset risk.
10. detecting system according to claim 8 or claim 9, wherein, egg described in the sample of the detection from test individual
The reagent material and/or instrument and equipment of casamino acid site and/or gene loci include：
In the amino acids of protein level detection EVI5 albumen the 354th, the amino acids of APOB albumen the 3768th and/or PKD1L3 eggs
The reagent material of white 1572nd amino acids；And/or
In DNA level, rs117711462, APOB gene rs376825639 and/or PKD1L3 of rna level detection EVI5 genes
Gene rs17358402 reagent material.
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