JP2013234981A - Method of simply classifying or determining phenotype of dyslipidemia or hyperlipemia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simply classify or determine the phenotype of dyslipidemia or hyperlipemia from the amount and quality of lipoprotein.SOLUTION: A fraction percentage and absorbance of a concentration waveform obtained in polyacrylamide gel disk electrophoresis, a quantitative value of total cholesterol obtained in a biochemistry autoanalyzer, or the like, are used as an algorithm, to enable simply and very easy classification or determination of V-type hyperlipemia, III-type hyperlipemia, IIa-type hyperlipemia, IIb-type hyperlipemia, IV-type hyperlipemia, or I-type hyperlipemia.

Description

Detailed Description of the Invention

A field in which phenotypes of dyslipidemia or hyperlipidemia are classified or determined from the results of analysis of lipoproteins in human serum or plasma.

In 1965, Friedrickson et al. Reported that lipids in human serum or plasma were measured by chemical assay for neutral fat (triglyceride, TG) and total cholesterol (TC), and lipoprotein screen electrophoresis results There are five types of lipids of so-called hyperlipidemia patients who are abnormal as compared with normal subjects, and these types are named as type I, type IIa, type IIb, type III, type IV, and type V.
Later, the World Health Organization WHO inherited the lipid phenotype classification of hyperlipidemic patients as type I, type IIa, type IIb, type III, type IV, and type V, and is still regarded as a standard for the treatment of hyperlipidemia. (Non-Patent Document 1).

In Japan as well, we initially attacked type I, type IIa, type IIb, type III, type IV, and type V, which are phenotype classification or type determination of hyperlipidemic individuals with WHO (Non-patent Document 5). However, in 2002, the Japanese Society for Arteriosclerosis published “Guidelines for the Treatment of Arteriosclerotic Diseases” (Non-Patent Document 2). Apart from the hyperlipidemia phenotype, 1) hypercholesterolemia, 2) high LDL Clinical guidelines for cholesterolemia, 3) low HDL cholesterolemia, and 4) hypertriglyceridemia were established. In the revised version of 2007, the term “hyperlipidemia” was determined to be inappropriate because the name “hypocholesterolemia” was used in the 2002 edition (Non-patent Document 3). .

In Non-Patent Document 1, when the hyperlipidemia phenotype is determined by the presence or absence of chilomicron (CM), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and floating β-LP. Has been. On the other hand, Non-Patent Document 4 introduces the concentration waveform of polyacrylamide disc electrophoresis by the Sudan B pre-staining method and is denoted as Type I, Type II, Type IIB, Type III, Type IV, and Type V. In Japan, it has been introduced that the type of hyperlipidemia can be determined from the concentration waveform of polyacrylamide disc electrophoresis, the TC value, the TG value, and the apoprotein abundance ratio (Non-patent Document 5). In any case, fixed numbers and the like were not described in each type of determination method, and the determination was left to the doctor who examined.

In recent years, many powerful antihyperlipidemic drugs have been released, and lipid measurement methods have become more sophisticated. Among them, a concentration measurement method from an image (Patent Document 1) is used for analyzing a concentration waveform of polyacrylamide disk electrophoresis (Disc-PAGE method), and an analysis of lipoprotein is also reported by an image. , Doctors are able to make diagnoses while viewing lipid measured values (TC, TG, etc.), electrophoretic images and concentration waveforms by biochemical automatic analyzers for each patient (Non-Patent Document 6, Non-Patent Document 6, Patent Document 7). According to Non-Patent Document 7, lipoproteins are CM, VLDL, LDL, HDL, medium specific gravity lipoprotein (IDL, mid-band), which is an unstable lipoprotein called bad arteriosclerosis, and small particle LDL. It has been introduced that (small, dense LDL) can be easily detected. As a method for distinguishing these unstable lipoprotein IDL, small, dense LDL from normal LDL, a method called relative mobility (VLDL is set to 0 and HDL is set to 1 to specify some LDLs on the concentration waveform). (The ratio of the mobility of LDL) is useful (Non-Patent Document 7). According to this, the relative mobility of IDL is described as RM0.10 to 0.18, and the small and dense LDL are described as RM0.40 or more.

On the other hand, Patent Document 3 describes a method for analyzing lipoproteins by the HPLC method, and Patent Document 4 sets the agarose gel electrophoresis method by a concentration waveform obtained by performing TC staining and TG staining. According to the protocol, a hyperlipemia phenotype is automatically determined by a computer through a complicated determination route.

References

JP 2004-258014 A JP-A-2005-121619 JP-A-8-320313 JP-A-11-230937

Classification of Hyperlipidaemias and Hyperlipoproteinemias, Bull, WHO, vol. 43, p891-908, 1970 Guidelines for the treatment of arteriosclerotic diseases, 2002 edition Arteriosclerotic disease clinical practice guideline, 2007 edition, Japan Atherosclerosis Society Mniz, N: Measurement of Plasma Lipoprotein by Electrophoresis on Polyacrylamide gel. Clin. Chem, Vol. 23, no. 10. p1826-1833, 1977 Atsushi Shirai, Yasushi Saito: Hyperlipidemia, medicina vol. 26, no3, p410-414, 1989 Inoue Ikuo: Lipofor, Metabolic Syndrome, Shigehiro Katayama, Chugai Medical Co., p161-163, 2008 Nippon Medical News, 4527, p51-58, January 29, 2011 Medical and testing equipment / reagents, Vol. 33, no. 3. p399-402, 2010 Progress in Medicine, Vol. 32, no. 3, p133-135, 2012

It is said that hyperlipidemia has been renamed dyslipidemia according to the 2007 edition of the Arteriosclerosis Medical Care Guidelines for Arteriosclerosis given in Non-Patent Document 3, but hyperlipidemia is included in dyslipidemia. Most of the therapeutic drugs are said to be effective as hyperlipidemia such as hypercholesterolemia and hypertriglyceridemia. Doctors who provide medical care comprehensively diagnose and treat TC, TG, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C) and other measured values and the results of lipoprotein fractions. When treating dyslipidemia and hyperlipidemia (hyperlipidemia, etc.), there are some patients whose TC and TG values are reduced and normalized, but there are some patients who are unable to achieve a therapeutic effect. There have been many reports of hyperlipidemia due to genetic constitution and basic diseases such as diabetes and hypertension. Diagnosis based on hyperlipidemia or the like due to genetic or underlying disease is required to be treated as usual assuming a phenotype such as hyperlipidemia.

Although the 2007 edition of Arteriosclerotic Disease Clinical Practice Guideline of Non-Patent Document 3 includes descriptions of phenotypes such as hyperlipidemia, each of type I, type IIa, type IIb, type III, type IV, and type V No explanation is given. The inventors recognize that the conventional phenotypes such as hyperlipidemia have reduced the value of practical use due to the evolution of measurement methods and the diversification of therapeutic agents. TC, TG, HDL measured on a daily basis by the measurement results of the Disc-PAGE method and biochemical automatic analyzers, etc. -Quantitative values of C, LDL-C, apoprotein, etc. (how to measure the amount of lipids), as well as the results of comprehensive diagnosis of various hyperlipidemia and antidiabetic treatment results, the concentration of the Disc-PAGE method From the waveform and TC measurements, we have discovered and put to practical use a method that allows anyone to classify and determine phenotypes such as hyperlipidemia in a very simple manner.

In order to practice the means to solve the problem, the method for determining the concentration from the image of Patent Document 1 can be applied to the analysis of human lipoprotein (Patent Document 2) together with the polyacrylamide gel disc electrophoresis method (Disc-PAGE method). A method for classifying or determining a new phenotype such as hyperlipidemia using the obtained concentration waveform is described.

The Disc-PAGE method is a measurement method that separates and analyzes lipoproteins according to particle size, and is known as a lipid quality test method. There are unique concentration waveforms for type V hyperlipidemia and type III hyperlipidemia. Although it was said to appear (Non-Patent Document 5), there were no criteria for its determination. The separation gel shown in Non-Patent Document 8 was a ready-made 3% lipoprotein assay kit “Lipophor AS” using a lipid prestaining method. The results analyzed using the kit of Non-Patent Document 8 are analyzed from the cathode side into CM, VLDL, IDL, LDL, small, dense LDL, and HDL. Among them, VLDL, IDL, LDL, small, dense LDL, and HDL are illustrated in the concentration waveform and are a system that reaches the doctor's hand as a report and is used for daily medical care. A test kit called Lipophor AS in Non-Patent Document 7 is known as a kit representing endogenous lipoprotein, and it has been reported that the VLDL% value has a good correlation with the TG value.

Inventors have argued that hyperlipidemia patients and diabetic patients are in mind that most patients with hyperlipidemia and diabetics are already treated for hyperlipidemia and diabetes. About 10,000 people have been evaluated for phenotypes such as hyperlipidemia. Despite selection of patients with hyperlipidemia, etc., whose concentration waveform of the Disc-PAGE method was different from the group of normal lipids, despite the treatment of hyperlipidemia, etc. Based on these findings, we discovered an algorithm that determines each type of hyperlipidemia.
In determining an algorithm such as hyperlipidemia, the metabolism of lipoproteins is mainly divided into endogenous lipoproteins and exogenous lipoproteins, and the determination of phenotype may be confused unless they are distinguished.
Endogenous lipoproteins are substances produced, secreted and metabolized mainly in the liver, and are a group of VLDL, IDL, LDL, small, dense LDL, and HDL. Of these, VLDL, which has the largest particle size, has a particle size of about 40 nm at most. Therefore, it is always called milky serum, in other words, milk serum after blood has been collected and serum separated just because VLDL is large. It will not be in a state. Milk milk serum appears when CM or CM remnant present in exogenous lipoprotein is present. It is said that CM and CM remnants have large particle sizes and may exceed 100 nm. If the minimum wavelength of visible light is 300 nm, CM and CM remnants will partially block visible light transmission. In particular, a phenomenon that serum becomes cloudy, that is, milk serum appears. In fact, we confirmed that volunteers had no milk in the serum without breakfast, and blood samples were taken at regular intervals after meals and examined for properties. After 2 or 3 hours after meals, they became milk serum. However, these people have confirmed that there is no change in the group of IDL, LDL, small, dense LDL, and HDL, although the amount of VLDL is slightly increased. Based on the above, it was determined that the presence of milk serum was deeply related to exogenous lipoprotein metabolism. When lipoproteins are discussed at the level of serum lipids, it is written in textbooks that dairy serum becomes high when the measured value of TG is high, but this is incomplete. Since TG is also present in large amounts in CM and CM remnants, it is because it was believed that patients with high TG were milk serum when viewed only from general biochemical quantitative values. Actually, TG is high in most cases of milk serum, but conversely, it is not milk serum because of high TG. Therefore, when discussing phenotypes such as hyperlipidemia, it has been found that accurate determination cannot be made when proceeding based on the TG value. I made it.

In the Disc-PAGE method, type V hyperlipidemia is said to have high TG, CM, and VLDL and low values of IDL, LDL, small, dense LDL, but there was no clear standard. We have set an algorithm of type V hyperlipidemia from a number of test results.
Algorithm for type V hyperlipidemia 1) The fraction of VLDL is 30% or more in the lipoprotein concentration waveform.
2) The peak value of the concentration waveform of IDL, LDL, small, dense LDL or the absorbance OD value at the maximum position in the set range is 0.1 or less, respectively.
3) The fraction% of HDL is 10% or more.
Note that a fractional fraction of VLDL of 30% or more indicates that the TG value of a patient who is not milk serum is approximately 200 mg / dL (Non-patent Document 7), and IDL, LDL, small, dense. The fact that the concentration waveform of LDL is thin was expressed by an absorbance OD value of 0.1 or less.

For type III hyperlipidemia, an algorithm of type III hyperlipidemia was set, centering on the presence of IDL that exhibits the same behavior as Floating β-LP as described in Non-Patent Document 1.
Algorithm for Type III Hyperlipidosis 1) The fraction of VLDL in the lipoprotein concentration waveform is 30% or more.
2) The peak value of the concentration waveform of LDL, small, dense LDL or the absorbance OD value at the maximum position in the set range is 0.1 or less, respectively.
3) The IDL fraction% is 10% or more.
Note that type III hyperlipidemia is characterized by the appearance of IDL by the Disc-PAGE method. This application has a fraction% of IDL of 10% or more, and other LDL and small, dense LDL. It was decided that the light absorbance waveform OD value was 0.1 or less. Furthermore, it is said that type III hyperlipidemia is essential to confirm the presence of apoprotein E2 by apo-E genotype or pheno-type test. I didn't get into the algorithm.

Type II hyperlipidemia refers to a state in which TC is high and TG is relatively low, and is classified into type IIa and type IIb based on the abundance of TG. Since the amount of TG also increases in milk serum, as described above, the algorithm of type IIa hyperlipidemia was set in the present application from the fraction% of VLDL and the TC value.
The cut-off of the quantitative value of TC was set to 220 mg / dL or more, which is the criterion for hypercholesterolemia described in Non-Patent Document 2 and Non-Patent Document 3.
Type IIa hyperlipidemia algorithm 1) The fraction of VLDL is less than 15% in the lipoprotein concentration waveform.
2) The quantitative value of TC is 220 mg / dL or more.
In general, type IIa hyperlipidemia is a patient who has few unstable lipoprotein IDL, small, dense LDL in the Disc-PAGE method and does not show abnormal lipid quality in the lipoprotein concentration waveform. Here, the quantitative value of TC was 220 mg / dL or more, and the fraction of VLDL was less than 15% of the upper limit of normal.

Type IIb hyperlipidemia is a case where the fractional value of VLDL is slightly higher than that of type IIa hyperlipidemia, and a portion that does not overlap with type IV hyperlipidemia was set.
Type IIb hyperlipidemia algorithm 1) The fraction of VLDL is 15-25% in the lipoprotein concentration waveform.
2) The quantitative value of TC is 220 mg / dL or more.
The difference between type IIb hyperlipidemia and type IIa hyperlipidemia was distinguished by the fractional% value of VLDL.

Type IV hyperlipidemia is said to be a case where the quantitative value of TC is low and the quantitative value of TG is high, but the boundary is not clear. Recently, a number of treatments that lower TC and TG levels have been released. During treatment, there are many cases where type IV changes to type IIa or IIb and vice versa, and it is difficult to determine type such as hyperlipidemia. There were many.
We invented about 10,000 concentration waveforms in the Disc-PAGE method, and derived the algorithm of type IV hyperlipidemia from their characteristics.
Type IV hyperlipidemia algorithm 1) Not hyperlipidemia of type V or type III and type IIb.
2) The fraction fraction of VLDL is 20% or more in the lipoprotein concentration waveform.
In addition, there is no standard for TC value in the determination of type IV hyperlipidemia, it is determined that it does not belong to type V, type III, type IIa or type IIb hyperlipidemia, and the fractional percentage of VLDL is 20% or more. Although the fractions of VLDL fractions of type IIb hyperlipidemia partially overlapped, it was considered appropriate because there were many patients who reciprocally changed from type IV to type IIb during treatment.

In the Disc-PAGE method, IDL and small, dense LDL, which are unstable LDL in the process of lipoprotein metabolism, are described above. In type IV hyperlipidemia, in addition to phenotypic determination, unstable lipoproteins It is possible to determine the appearance of proteins together, and the determination algorithm is set so that IDL and small, dense LDL can be distinguished from those that do not exist. First, type IV hyperlipidemia with increased IDL was set as follows.
Algorithm of type IV hyperlipidemia with increased IDL 1) Not V or type III and type IIb hyperlipidemia etc.
2) The fraction fraction of VLDL is 20% or more in the lipoprotein concentration waveform.
3) The IDL fraction% is 10% or more.
Type IV hyperlipidemia often appears as IDL, small, dense LDL, which is said to be unstable and is a risk substance for arteriosclerosis. In order to clarify the existence of this dangerous substance related to arteriosclerosis, we invented an algorithm of type IV hyperlipidemia with an increase in IDL. IDL is said to be present in about 5% even in normal lipids (Non-patent Document 9), so that the existence of IDL can be more reliably distinguished and the existence of IDL is more reliably limited when the IDL fraction is 10% or more. Type IV hyperlipidemia with increased IDL.

Similarly, type IV hyperlipidemia with increased small and dense LDL was set as follows.
Algorithm of type IV hyperlipidemia with increased small, dense LDL 1) No hyperlipidemia of type V or type III and type IIb.
2) The fraction fraction of VLDL is 20% or more in the lipoprotein concentration waveform.
3) The fraction% of small, dense LDL should be 6% or more.
In addition, since small and dense LDL said here refers to relative mobility RM0.40 or more (nonpatent literature 7), the part of relative mobility RM0.35 described in nonpatent literature 9 is also small, dense LDL. Based on the fact that it is written that the existence of ssl is suspected, the fraction% of small, dense LDL was determined to be 6% or more.

Type IV hyperlipidemia with an increase in both IDL and small, dense LDL was set as follows.
IDL, small, dense Type IV hyperlipidemia algorithm with increased LDL 1) No hyperlipidemia of type V or type III and type IIb.
2) The fraction fraction of VLDL is 20% or more in the lipoprotein concentration waveform.
3) The fraction% of IDL is 10% or more, and the fraction% of small, dense LDL is 6% or more.

Type I hyperlipidemia is a disease in which lipoprotein lipase is deficient or very low, and VLDL and other endogenous lipoprotein metabolism does not progress in the liver. CM and CM remnants accumulate in the blood and sometimes cause pancreatitis. is there. If CM or CM remnant is present, laboratory technicians often add comments such as milk + or milk +++ to the report, and notice whether CM or CM remnant is present or loading, which is the sample addition part of the Disc-PAGE method. The dark blue color remained on the gel, and even if you look at the report with an image of Patent Document 1, you noticed the presence of CM and CM remnant, so I did not dare put milk serum information into the algorithm of type I hyperlipidemia.
Type I hyperlipidemia algorithm 1) The peak values of IDL, LDL, small, dense LDL, and HDL are each OD 0.03 or less.
Since type I hyperlipidemia indicates that almost no concentration waveforms of IDL, LDL, small, dense LDL, and HDL are observed, the inventors set the concentration to OD 0.03 or less.

Up to the previous section, as a means to solve the problem, the method of classifying or judging the phenotype such as hyperlipidemia has been described by taking the measurement result by the Disc-PAGE method as an example. Analysis of HPLC No. 3, agarose gel electrophoresis method or flat plate slab electrophoresis method of Patent Document 4, density gradient type gradient gel electrophoresis method and the like.
Since these are different in analysis principle from the Disc-PAGE method, the shape of the concentration waveform, the fraction%, and the name of the lipoprotein may change. For example, in the agarose gel electrophoresis method, pre-β, β, and α lipoproteins are separated and analyzed from the cathode, and when CM is present, the pre-β and β portions become broad (floating β-LP). pre-β is also called VLDL, β is also called LDL, and α is also called HDL.
As mentioned above, it was pointed out that exogenous lipoproteins may be mixed in the determination of phenotypes such as hyperlipidemia, but agarose gel electrophoresis does not distinguish between exogenous and endogenous lipoproteins. Since it is analyzed, separation is a little unclear, but it is used daily because of its low cost.
In addition, when TC staining or TG staining of Patent Document 4 is used, pre-β-cholesterol (or triglyceride), β-cholesterol (or triglyceride), and α-cholesderol (or triglyceride) are obtained. It can also be called LDL cholesterol (or triglyceride) or HDL cholesterol (town triglyceride). Since the present invention can determine a phenotype such as hyperlipidemia with a very simple algorithm, the present application can be performed by various measuring methods if the expression and numerical values are changed somewhat according to the HPLC method and the agarose gel method. Needless to say, it can be used to determine a phenotype such as hyperlipidemia.

Once the algorithm that determines the phenotype such as hyperlipidemia is clear, the algorithm is programmed in advance on a computer and the phenotype such as hyperlipidemia is automatically printed when the test report is created. Can do.

Recently, a wide variety of drugs for treating hyperlipidemia are sold and used in large quantities for the treatment of hyperlipidemia and the like. As a result, if the hyperlipidemic state is resolved, it tends to be a good treatment, but the patient's condition varies, and it is the doctor's exclusive right to decide which drug and how much to use. In making this diagnosis and treatment, the doctor makes a diagnosis and treats the patient's individual lipid metabolism by referring to the TC value, TG value, LDL-C value, and lipoprotein electrophoresis results. Diagnosis considers genetic or background diseases such as diabetes and hypertension, but the current lipid status of the patient being treated may be normal in the next month even if it is type IV hyperlipidemia. You may have type hyperlipidemia. Therefore, the selection of therapeutic agents must be appropriately selected and administered with reference to the patient's constitution and phenotype such as hyperlipidemia.

Until now, there was no standard for showing numerical values in phenotypes such as hyperlipidemia, so doctors had chosen phenotypes based on experience and prescribed treatment drugs. However, according to the present invention, it is said that determination of a new phenotype such as hyperlipidemia in a patient undergoing hyperlipidemia treatment is difficult even for a specialist doctor, and a test report of TC value and lipoprotein electrophoresis The ability to easily determine a phenotype such as hyperlipidemia based on the concentration waveform in the book can eliminate the risk of diagnosis even without being a specialist. As a result, there is no doubt that the use of the present invention can greatly contribute to selection of therapeutic agents and daily management of patients.

Is an example of a report containing a concentration waveform of a patient with type A hyperlipidemia A.

Is an example of a report containing a concentration waveform of type IV hyperlipidemia patient B with increased IDL.

Is an example of a report containing a concentration waveform of a type IIa hyperlipidemic patient C.

In FIG. 1, (1) is a concentration waveform of electrophoresis of the lipoprotein of patient A, and (2) is a solid waveform, and a standard sample is a concentration waveform of a normal lipid person. The scale on the vertical axis in (3) is a portion indicating that the OD of the optical density absorbance is 0.1. (4) is VLDL, (5) is IDL, (6) is LDL, (7) is small, dense LDL, (8) is each concentration waveform of HDL, (9) is the area ratio of each concentration waveform. Indicates. (10) is the TC value of patient A. The fraction% of VLDL from waveform 1 is 51%, and the peak value of the concentration waveform from IDL to small, dense LDL or the absorbance OD value at the maximum position within the set range are both 0.1 or less, and the HDL fraction % Was 14%, and this example was judged as type V hyperlipidemia. An engineer accustomed to the Disc-PAGE method is a typical pattern that can be predicted as a V-type just by looking at the electrophoretic image. However, quantifying the determination method in terms of eliminating individual errors in measurement and determination worth it.

In FIG. 2, (11) shows the concentration waveform of the lipoprotein electrophoresis of patient B, and (14) shows the area ratio of each concentration waveform. (12) in FIG. 2 is VLDL of patient B, the fraction of which is 22% as shown in (14) and the fraction of IDL in (13) is from 11 to 11% (14) Since the peak height of the LDL in (15) is above the OD line of 0.1 and the TC value shown in (16) is 195 mg / dL, this example is an IV type with an increase in IDL. It was judged as hyperlipidemia.

(17) in FIG. 3 is an electrophoresis concentration waveform of lipoprotein of patient C, and (17) shows the area ratio of each concentration waveform. (18) shows that the TC value of patient C is 317 mg / dL, and that the fractional% value of VLDL in (19) is 9% from (17), so that type IIa high fat Judgment was made with blood.

Although not shown in the figure, type IIb hyperlipidemia is characterized by a higher fraction of VLDL than that of type IIa hyperlipidemia. From the correlation between TG and VLDL, we Was determined to be type IIb.

Type III hyperlipidemia is characterized by the fact that it can be generally judged by looking at the electrophoretic image and concentration waveform of the Disc-PAGE method together with type V hyperlipidemia. However, it is important to differentiate from type V hyperlipidemia. It becomes. The difference from type V hyperlipidemia was differentiated by having a fraction% of IDL of 10% or more in consideration of the fact that IDL is high and there is almost no LDL, small, dense LDL. In addition to this, as a definitive diagnosis of type III hyperlipidemia, it is needless to say that the presence of E2 must be confirmed by an apo E genotype or phenotype test, but it is not adopted as a simple criterion. It was limited to calling attention based on the statement “I suspected type III hyperlipidemia”.

(1) Concentration waveform of lipoprotein electrophoresis of patient A (2) Concentration waveform of normal lipid (3) Position where absorbance OD is 0.1 (4) VLDL
(5) IDL
(6) LDL particle marker (7) small, dense LDL
(8) HDL
(9) Concentration waveform area ratio (10) Patient A TC value (11) Patient B lipoprotein electrophoresis concentration waveform (12) Patient B VLDL
(13) Patient B's VIDL
(14) Area ratio of concentration waveform of patient B (15) LDL of patient B
(16) TC value of patient B (17) Area ratio of concentration waveform of patient C (18) TC value of patient C (19) VLDL of patient C

Claims (11)

High-low density lipoprotein VLDL, medium density lipoprotein IDL, low density lipoprotein LDL calculated by polyacrylamide gel disc electrophoresis, which is an analysis method that separates and analyzes lipoproteins in a subject and expresses the result as a concentration waveform, Small particle lipoprotein small, dense LDL, fraction of high specific gravity lipoprotein HDL, IDL, LDL, small, dense LDL and HDL concentration waveform peak value or absorbance OD value at the maximum position in the set range and raw A method for easily classifying or determining a phenotype of dyslipidemia or hyperlipidemia using a quantitative value of total cholesterol TC in the subject measured by an automatic chemical analyzer or the like The VLDL fraction% in the lipoprotein concentration waveform is 30% or more and the HDL fraction% is 10% or more, and the peak value of the concentration waveform of IDL, LDL and small, dense LDL or the maximum in the set range 2. The dyslipidemia or hyperlipidemia phenotype according to claim 1, wherein the position absorbance OD value is 0.1 or less, and the phenotype of dyslipidemia or hyperlipidemia according to claim 1 is classified. How to judge The fraction of VLDL in the lipoprotein concentration waveform is 30% or more, and the peak value of the concentration waveform of LDL, small, and dense LDL or the absorbance OD value at the maximum position within the set range are both 0.1 or less 2. The method for easily classifying or determining a dyslipidemia or hyperlipidemia phenotype according to claim 1, wherein the fraction of IDL is 10% or more, and is defined as type III hyperlipidemia. IIa type high fat having a fractional% of VLDL in a lipoprotein concentration waveform of less than 15% and a total cholesterol value TC measured by a biochemical automatic analyzer or the like is not less than 220 mg / dL A method for easily classifying or determining a phenotype of dyslipidemia or hyperlipidemia according to claim 1 characterized by IIb has a fractional fraction of VLDL in the lipoprotein concentration waveform of 15 to 25% and a total cholesterol value TC measured by a biochemical automatic analyzer or the like is 220 mg / dL or more. A method for easily classifying or determining a dyslipidemia or hyperlipidemia phenotype according to claim 1, characterized in that the type is hyperlipidemia The fraction of VLDL in the lipoprotein concentration waveform is 20% or more, type V hyperlipidemia of claim 2, type III hyperlipidemia of claim 3, and type IIb hyperlipidemia of claim 5 The method for easily classifying or determining the dyslipidemia or hyperlipidemia phenotype according to claim 1, wherein the type IV hyperlipidemia 7. The dyslipidemia or hyperlipidemia phenotype according to claim 1, wherein the fraction of IDL is 10% or more, whereby the type IV hyperlipidemia is accompanied by an increase in IDL. Simple classification or judgment method 7. The hyperlipidemia or hyperlipidemia according to claim 1, wherein the fraction% of small, dense LDL is 6% or more, whereby type IV hyperlipidemia is accompanied by an increase in small, dense LDL. Method for easily classifying or determining the phenotype of septicemia In claim 6, when the fraction% of IDL is 10% or more and the fraction% of small, dense LDL is 6% or more, it is considered to be type IV hyperlipidemia accompanied by an increase in IDL and small, dense LDL. A method for easily classifying or determining a phenotype of dyslipidemia or hyperlipidemia according to claim 1 In the lipoprotein concentration waveform, there is no IDL, LDL, small, dense LDL, or HDL waveform, or the peak value of the concentration waveform or the absorbance OD value at the maximum position in the set range are all 0.03 or less. A method for easily classifying or determining a dyslipidemia or hyperlipidemia phenotype according to claim 1, characterized in that the type is hyperlipidemia The algorithm according to claim 2 to claim 10 is stored in a computer, and the result of phenotype obtained by individual calculation processing for each specimen is generated as a lipoprotein fraction test report. 2. A method for easily classifying or determining a dyslipidemia or hyperlipidemia phenotype according to claim 1, wherein the phenotype is dyslipidemia or hyperlipidemia according to claim 1.

Images