WO2021029462A1 - Composition for prediction or diagnosis of hypertension or obesity - Google Patents

Abstract

The present invention relates to a composition that comprises a preparation that measures the methylation level of the promoter region of the natriuretic peptide receptor 2 (NPR2) gene, and thus can predict or diagnose hypertension or obesity even when a symptom thereof is not identified visually or from other results, or even at a very early stage.

Description

Composition for predicting or diagnosing hypertension or obesity

The present invention relates to a composition for predicting or diagnosing hypertension or obesity.

Hypertension refers to the case where the systolic blood pressure is 140mmHg or more or the diastolic blood pressure is 90mmHg or more.The symptoms are headache, dizziness, palpitations, dyspnea, sleep problems, hemiplegia, arteriosclerosis, etc. According to the data presented by the National Hypertension Center, the cause of primary hypertension (essential hypertension), which accounts for the majority of 90% of hypertension, is not yet clear, but race, age, family history, obesity, lack of exercise, smoking, Many factors, including diet, cause disease, and secondary hypertension accounts for 10%, and it is reported that it is caused by specific causes such as endocrine system disease, aortic stenosis, kidney disease, and drugs.

Obesity occurs when energy intake exceeds energy consumption over a long period of time and excess energy is stored in fat. Under normal conditions, appetite is regulated by factors derived from the periphery, of which leptin and insulin are representative. When the weight is increased, the concentration of leptin and insulin in the blood increases, and it acts on the hypothalamus, the feeding center, to suppress appetite and promote energy consumption to restore the increased weight. This normal feedback system that regulates energy balance is a kind of protective mechanism that prevents weight gain, but in obesity, because the feedback system does not work properly, obesity worsens and causes comorbidities.

Recently, methods for diagnosing diseases such as cancer through DNA methylation measurement have been proposed. When the CpG island of a specific gene is hypermethylated, the expression of that gene is blocked (gene silencing). This is the main mechanism in which the function of the gene is lost even without mutation in the protein-specific coding sequence of the gene in vivo. In particular, the function of a number of tumor suppressor genes is lost in cancer. It is interpreted as a cause. Therefore, searching for methylation of CpG islands of a specific gene is of great help in disease research, and attempts to use it for diagnosis and screening of diseases by examining this by methods such as methylation-specific PCR or automatic base analysis have been actively made in recent years. .

In the genomic DNA of mammalian cells, in addition to A, C, G, and T, the fifth base is present, which is 5-methylcytosine (5-mC) with a methyl group attached to the fifth carbon of the cytosine ring. 5-mC always comes only to the C of the CG dinucleotide (5'-mCG-3'), and this CG is often referred to as CpG. Most of C in CpG is methylated with a methyl group attached. This methylation of CpG inhibits the expression of repetitive sequences in the genome, such as Alu and transposon, and is the most common site of extragenic changes in mammalian cells. The 5-mC of CpG is naturally deaminated and converted to T, and accordingly, CpG in the mammalian genome only has a frequency of 1%, which is much lower than the normal frequency (1/4 x 1/4 = 6.25%). Show.

Some of the CpGs appear exceptionally densely, and they are called CpG islands. CpG islands are 0.2~3kb in length, the distribution percentage of C and G bases exceeds 50%, and the distribution percentage of CpG is higher than 3.75%. About 45,000 CpG islands appear in the whole human genome, and they appear especially concentrated in the promoter region that controls the expression of genes. On the other hand, in the somatic cell of a normal person, the CpG islands of these important gene expression control sites are not methylated, but the imprinted genes and inactivated genes on the X chromosome are methylated so that they are not expressed during development. .

Many diseases are caused by genetic abnormalities, and the most common form of genetic abnormalities is a change in the coding sequence of a gene, and such genetic changes are called mutations. When there is a mutation in a gene, the protein that the gene encodes changes structure and function, resulting in disorders and defects, and these mutant proteins cause disease. However, even without mutations in a specific gene, an abnormality in the expression of that gene can cause disease. A typical example is methylation, in which a methyl group is attached to the cytosine base site of the CpG island, the regulatory site of gene transcription, in which case the gene is blocked from expression. This is called epigenetic change, and it is transmitted to progeny cells like a mutation, and causes the same effect, that is, loss of expression of the corresponding protein.

There have been some techniques for diagnosing or predicting specific cancers by analyzing the methylation level of a gene, but there have been no reports of studies that accurately predict or diagnose obesity and hypertension through the analysis of methylation levels of specific genes.

An object of the present invention is to provide a composition capable of predicting and diagnosing hypertension or obesity with high accuracy.

An object of the present invention is to provide a method of predicting and diagnosing hypertension or obesity with high accuracy and providing information necessary for diagnosis.

1. A composition for predicting or diagnosing hypertension or obesity, comprising an agent for measuring the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene consisting of the sequence of SEQ ID NO: 1.

2. In the above 1, a primer set capable of amplifying a fragment containing the NPR2 gene promoter region consisting of the methylated nucleotide sequence of SEQ ID NO: 1, and hybridizing with the NPR2 gene promoter region consisting of the methylated nucleotide sequence of SEQ ID NO: 1 Probe, methylation specific binding protein capable of binding to the NPR2 gene promoter region consisting of methylated nucleotide sequence of SEQ ID NO: 1, methylation specific binding antibody or aptamer, sequencing primer, sequencing bi-synthesis primer and sequencing bi-ligation At least one composition selected from the group consisting of primers.

3. The composition of the above 1, wherein the formulation comprises a primer set consisting of the sequence of SEQ ID NO: 2 and 3.

4. The composition of 1 above, wherein the methylation site is the cytosine of 257, 264, 266 or 270 in the sequence of SEQ ID NO: 1.

5. In the above 1, the predicted disease is obesity, and the methylation site is a cytosine at position 158, 213, 218, 228, 253, 257, 261, 264, 266, 270 or 281 in the sequence of SEQ ID NO: 1 , Composition.

6. A kit for predicting or diagnosing hypertension or obesity comprising the composition of any one of the above 1 to 5.

7. Information for predicting or diagnosing hypertension or obesity, comprising comparing methylation of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene consisting of the sequence of SEQ ID NO: 1 from the isolated biological sample with the methylation of a normal control sample Delivery method.

8. The method of 7 above, further comprising the step of detecting methylation of the promoter region of the NPR2 gene from the biological sample.

9. The method of 7 above, wherein the methylation site is the cytosine of 257, 264, 266 or 270 in the sequence of SEQ ID NO: 1.

10. In the above 7, the predicted disease is obesity, and the methylation site is a cytosine at position 158, 213, 218, 228, 253, 257, 261, 264, 266, 270 or 281 in the sequence of SEQ ID NO: 1 , Way.

11. The method of the above 7, wherein when the methylation level obtained from the sample is higher than the methylation level of the normal control sample, it corresponds to hypertension or obesity, or provides information that the onset is high.

12. Comparing the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene consisting of the sequence of SEQ ID NO: 1 in the sample isolated from the individual before and after feeding the subject diet; And

When the methylation level is reduced after diet feeding, selecting a diet for improving obesity or hypertension as a diet for improving obesity or hypertension.

13. The method of 12 above, wherein the methylation site is a cytosine at position 257, 264 or 270 in the sequence of SEQ ID NO: 1.

14. The method of 12 above, wherein the target disease is obesity, and the methylation site is a cytosine at position 213, 218, 228, 257, 264, 270 or 281 in the sequence of SEQ ID NO: 1.

The present invention can predict obesity or hypertension at an early stage, or predict the onset degree with high accuracy.

1 is a graph showing a change in the methylation level of the promoter region of the NPR2 gene in the obese group and the hypertensive group. (a) is a comparison between a traditional Korean food group and a westernized Korean food group, (b) is a comparison between a normal group and an obese group, and (c) is a comparison between a normal group and a hypertensive group.

Hereinafter, the present invention will be described in detail.

The present invention relates to a composition for predicting or diagnosing hypertension or obesity.

The composition for predicting or diagnosing hypertension or obesity of the present invention includes an agent for measuring the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene.

The promoter of the NPR2 gene is a sequence including a CpG island, and may be formed of the nucleotide sequence of SEQ ID NO: 1, but is not limited thereto. The nucleotide sequence of SEQ ID NO: 1 is a sequence including a CpG island, and is a base at positions 35,791,398-35,791,820 of chromosome 9 in the UCSC Genome Browser Human GRCh37/hg19 DNA sequence.

The level of methylation can be measured on genomic DNA obtained from a biological sample isolated from an individual.

The individual may be a subject suspected of obesity or high blood pressure, a subject for which obesity or high blood pressure risk is to be predicted. This may be a mammal, including a human, and specifically may be a human.

The sample may be, for example, one or more selected from the group consisting of cells, tissues, biopsies, paraffin tissue, blood, serum, plasma, urine, and combinations thereof, and more preferably blood, but is not limited thereto.

The agent for measuring the methylation level is, for example, a primer set capable of amplifying a fragment containing the NPR2 gene promoter region consisting of the methylated nucleotide sequence of SEQ ID NO: 1, the NPR2 gene promoter region consisting of the methylated nucleotide sequence of SEQ ID NO: 1 Probe capable of hybridizing with, methylation specific binding protein capable of binding to the NPR2 gene promoter region consisting of the methylated nucleotide sequence of SEQ ID NO: 1, methylation specific binding antibody or aptamer, sequencing primer, sequencing bi-synthesis primer and sequencing It may be a bi-ligation primer or the like.

Specifically, a primer set containing the sequences of SEQ ID NOs: 2 and 3 can be used, and more specifically, a primer set consisting of the sequences of SEQ ID NOs: 2 and 3 can be used.

The methylation site may be, for example, a cytosine at position 158, 213, 218, 228, 253, 257, 261, 264, 266, 270 or 281 in the sequence of SEQ ID NO: 1, but is not limited thereto.

According to an embodiment of the present invention, it may be a cytosine at position 257, 264, 266 or 270 in the sequence of SEQ ID NO: 1, and also, 213, 218, 228, 257, 264, 270 or 281 in the sequence of SEQ ID NO: 1 It may be a cytosine at position 1, or a cytosine at position 257, 264, or 270, but is not limited thereto.

By measuring the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene with the composition of the present invention, when the methylation level is measured higher than that of the normal group, it can be determined that it corresponds to hypertension or obesity, or has a high possibility of onset.

In addition, the present invention relates to a kit for predicting or diagnosing hypertension or obesity comprising the composition.

The kit of the present invention includes a composition containing a substance capable of detecting whether the NPR2 gene promoter region consisting of the nucleotide sequence of SEQ ID NO: 1 is methylated, and targets a sample isolated from a biological sample, the NPR2 gene promoter region By detecting the methylation of hypertension or obesity can be predicted or diagnosed.

The sample may be within the above-described range, and a genomic DNA sample isolated therefrom may be used. It is preferable that the genomic DNA sample is CpG-containing. Typically, the CpG-containing nucleic acid is DNA, but is not limited thereto, and may include a sample containing DNA or RNA including DNA and mRNA. Here, the DNA or RNA may be single-stranded or double-stranded, or may contain a DNA-RNA hybrid.

The kit of the present invention comprises a compartmentalized carrier means containing a sample, a second container containing a primer capable of amplifying the 5'-CpG-3' sequence site of the sample, and a truncated or cleaved nucleic acid for amplifying a methylated CpG-containing nucleic acid It may comprise one or more containers comprising a third container containing means for detecting the presence of non-reactive nucleic acids. In one embodiment, the primer is PCR for detecting whether methylation has occurred on the genome, methylation specific PCR, real time methylation specific PCR, and methylated DNA specific binding protein. It may be a primer for use in PCR using PCR, PCR using a methylated DNA specific binding antibody or aptamer, quantitative PCR, nucleic acid chip, sequencing, sequencing bi-synthesis, or sequencing bi-ligation. The carrier means are suitable for containing one or more containers, such as bottles, tubes, and each container contains independent components used in the method of the invention. In the specification of the present invention, a person of ordinary skill in the art can easily dispense the necessary agent in a container.

In addition, the present invention relates to a method of providing information for predicting or diagnosing hypertension or obesity.

The present invention includes comparing the methylation of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene from the isolated biological sample with that of a normal control sample.

The biological sample and the subject subject may be within the aforementioned range.

When the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene is higher than the methylation level of the normal control sample, information indicating that it corresponds to hypertension or obesity or is likely to develop may be provided.

The methylation site may be, for example, a cytosine at position 158, 213, 218, 228, 253, 257, 261, 264, 266, 270 or 281 in the sequence of SEQ ID NO: 1, but is not limited thereto.

According to an embodiment of the present invention, it may be a cytosan at position 257, 264, 266, or 270 in the sequence of SEQ ID NO: 1, and also, 213, 218, 228, 257, 264, 270 or 281 in the sequence of SEQ ID NO: 1 It may be a cytosine at position 1, or a cytosine at position 257, 264, or 270, but is not limited thereto.

The method of the present invention may further include detecting methylation of the promoter region of the NPR2 gene from the biological sample.

More specifically, this may be performed by separating genomic DNA from a biological sample, treating methylated DNA and unmethylated DNA in genomic DNA with a reagent that changes differently, and detecting methylation, but is not limited thereto.

The reagent for differently modifying the methylated DNA and the unmethylated DNA may be, for example, bisulfite, disulfite, hydrogen sulfite, but is not limited thereto.

The unmethylated cytosine (C) base on bisulfite-treated DNA is deaminated to change to a uracil (U) base, while the methylated cytosine base remains as cytosine. That is, they are labeled with different bases so that they can be distinguished from each other according to the presence or absence of methylation of cytosine bases on DNA by bisulfite treatment.

The detection of methylation is, for example, bisulfite sequencing, sequencing by synthesis, sequencing by ligation, methylation specific PCR, and real time methylation specific PCR. ), PCR using a methylated DNA specific binding protein, PCR using a methylated DNA specific binding antibody or an aptamer, or a nucleic acid chip, but is not limited thereto.

The bisulfite sequencing method is a method of detecting a nucleic acid containing methylated CpG, the step of contacting a sample containing the nucleic acid with an agent that modifies an unmethylated cytosine, and the CpG-of the sample using a methylation-independent oligonucleotide primer. And amplifying the containing nucleic acid. Here, the oligonucleotide primer may be characterized by amplifying the nucleic acid without distinguishing between the modified methylated and unmethylated nucleic acids. The amplified product may be sequenced by the Sanger method using a sequencing primer or analyzed by a next generation sequencing (NGS) method to detect methylated nucleic acids.

Next-generation sequencing methods may be characterized by sequencing by synthesis and sequencing by ligation. The feature of this method is that instead of creating a bacterial clone, a single DNA fragment is spatially separated, amplified in situ (clonal amplification), and sequenced. At this time, since hundreds of thousands of fragments are read at the same time, it is also referred to as a massive parallel sequencing method. Basically, it is a sequencing bi-synthesis method, and it uses a method of obtaining a signal by sequentially attaching mono or dinucleotides, including pyro-sequencing, ion torrent, and Solexa methods.

NGS equipment based on Sequencing by Synthesis includes Roche's 454 platform, Illumina's HiSeq platform, Life Technology's Ion PGM platform, and Pacific BioSciences' PacBio platform. have. The 454 and Ion PGM use emulsion PCR as a clonal amplification method, and HiSeq uses bridge amplification. The sequencing bi-synthesis method reads the sequence by detecting phosphate, hydrogen ions, or previously attached fluorescence generated when DNA is synthesized by attaching one nucleotide in sequence. In the method of detecting the sequence, 454 uses a pyroseqeuncing method using phosphoric acid, and Ion PGM uses hydrogen ion detection. HiSeq and PacBio decode the sequence by detecting fluorescence.

Sequencing by ligation is a sequencing technology that uses DNA ligase to identify a nucleotide at a specific position in a DNA sequence. Unlike most sequencing techniques that use polymerases, they do not use polymerases, and DNA ligases do not ligate mismatched sequences. This is the SOLiD system. In this technique, two bases are read at intervals, and since each base is independently repeated five times through a primer reset, the accuracy is increased by reading each base twice.

In the case of sequencing-by-ligation, among a set of dinucleotide primers made of 16 combinations, dinucleotide primers corresponding to the nucleotide sequence are sequentially ligated, and the combination of these ligations is finally analyzed to determine the nucleotide sequence of the DNA. Completed.

In addition, the present invention relates to a method of selecting a diet for improving obesity or hypertension.

The method of the present invention comprises the steps of comparing the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene consisting of the sequence of SEQ ID NO: 1 in a sample isolated from an individual before and after feeding a subject diet; And if the methylation level is decreased after feeding the diet, selecting the diet as a diet for improving obesity or hypertension.

Subjects and samples may be within the above-described range.

The measurement of the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene can be performed using the above-described agent or by the above-described method.

The methylation site may be, for example, a cytosine at position 257, 264, or 270 in the sequence of SEQ ID NO: 1. Further, it may be a cytosine at position 213, 218, 228, 257, 264, 270, or 281 in the sequence of SEQ ID NO: 1, but is not limited thereto.

If the target diet is a diet for the target individual, the type is not limited, and may be, for example, a traditional Korean diet.

The diet may be fed once or several times, for example, one week or more, or two or more weeks, but is not limited thereto.

If the methylation level is decreased after feeding the diet, the diet may be selected as a diet for improving obesity or hypertension.

Hereinafter, examples will be described in detail to illustrate the present invention in detail.

Example

1. Sample preparation

The following test subjects were recruited, and genomic DNA was extracted from their blood samples and used for methylation analysis. A total of 104 people in the normal group, 44 people in the hypertensive group, and 80 people in the obese group were selected. A total of 5 people in the traditional Korean group and 5 people in the westernized Korean group were selected. The selection criteria for the hypertensive group and the obese group are shown in Tables 1 and 2 below, and detailed information is shown in Tables 3 and 4 below. And for the diet control group, the selection criteria are shown in Table 5, and detailed information is shown in Table 6.

2. Methylation Analysis

A total of 20 genomic DNA samples were selected before and after diet for 2 weeks for each of the 4 subjects in the normal group and the hypertensive group, and the group that consumed traditional Korean food and the group that consumed westernized Korean food for 2 weeks. bisulfite sequencing) was performed. The analysis of WGBS in the normal group and hypertensive group was performed by requesting Macrogen (Korea), and through the analysis of WGBS, regions with differences in methylation ratio in the normal group, hypertension group, and obese group were selected, and 104 samples of the normal group, Bisulfite sequencing was performed for the location of 44 samples in the hypertensive group and 80 samples in the obese group. The WGBS of the group who ate traditional Korean food and the group who ate Westernized Korean food was commissioned by Macrogen (Korea) and analyzed the results by the Korea Food Research Institute. Through this, regions with significant differences in the methylation rate were selected in the group who ate Westernized Korean food and the group who ate traditional Korean food after a two-week diet. For the location, bisulfite sequencing was performed on a total of 20 samples, 5 samples each before and after traditional Korean food, and 5 samples each for westernized Korean food. Bisulfite sequencing was performed by requesting LAS Co., Ltd. (Korea), and Illumina MiSeq. Platform was used. The reference sequence used for the analysis was Human GRCh37/hg19 from UCSC GenomeBrowser (http://genome.ucsc.edu/cgi-bin/hgGateway).

3. NPR2 gene promoter region (hg19:chr9:35,791,398-35,791,819) Assay between normal and obese groups through methylation analysis

Using the genomic DNA of the entire experimental subjects recruited for the promoter region of the NPR2 gene (normal group n=104, obese group n=80), methylation was confirmed. DNA methylation was increased in the obese group compared to the normal group at 11 cytosine positions (35,791,555 / 35,791,610 / 35,791,615 / 35,791,625 / 35,791,650 / 35,791,654 / 35,791,658 / 35,791,661 / 35,791,663 / 35,791,667 / 35,791,678).

1B is a BSAS analysis result of the NPR2 gene promoter region of the normal group (black) and the obese group (red), and 11 cytosine positions confirmed to show a significant difference in methylation level between the normal group and the obese group Is the same as the area marked with an asterisk.

The value was obtained using the methylation ratio (mean± SD), the p value was obtained using a general linear model that adjusted sex, age, smoking, and drinking, and the significance was confirmed at the p<0.05 level. As a result, among the 11 cytosine positions of the NPR2 gene promoter site, where the methylation level is significantly increased by the normal and obese groups, 10 cytosine positions excluding those at 35,791,650 were significantly correlated with the number of fast food intakes. It was confirmed that there is (Table 8).

4. NPR2 gene promoter region (hg19:chr9:35,791,398-35,791,819) Assay between group and hypertension group through methylation analysis

The methylation was confirmed using the genomic DNA of the entire experimental subjects recruited for the promoter region of the NPR2 gene (normal group n=104, hypertension group n=44). DNA methylation was increased in the hypertensive group compared to the normal group at the four cytosine positions (35,791,654, 35,791,661, 35,791,663, 35,791,667) (Table 9).

(C) of Figure 1 is the BSAS analysis results of the NPR2 gene promoter region of the normal group (black) and the hypertensive group (red), four confirmed that the methylation level shows a significant difference between the normal group and the hypertension group The cytosine location is the same as the site marked with an asterisk.

The value was calculated using a general linear model that adjusted the methylation ratio (mean± SD), and the p value was adjusted for sex, age, smoking, drinking, and BMI. Significance was confirmed at the p<0.05 level.

5. NPR2 gene promoter region (hg19:chr9:35,791,398-35,791,819) Assay between traditional Korean food intake group and Westernized Korean food intake group through methylation analysis

The composition characteristics of the Korean diet (K-diet) and the Westernized Korean food (control diet) consumed by the test subjects are shown in Table 10, and the diet was prepared based on the definition and characteristics of traditional Korean food specified in the following published paper. Constructed and provided. (SH Kim et al. Korean diet: Characteristics and historical background. J Ethn Foods. 2016;3:26-31)

Using the genomic DNA of the entire experimental subjects recruited for the promoter region of the NPR2 gene (traditional Korean group n=3, westernized Korean group n=4), methylation was confirmed. 19 Cytosine Locations (35,791,421 / 35,791,434 / 35,791,517 / 35,791,566 / 35,791,576 / 35,791,610 / 35,791,615 / 35,791,619 / 35,791,625 / 35,791,640 / 35,791,654 / 35,791,661 / 35,791,667 / 35,791 / 35,791,35,791 Korean / 35,791 / 35,791, Korean 35,791) DNA methylation was decreased in the group fed traditional Korean food compared to the group (Table 11).

Figure 1 (a) is a BSAS analysis result of the NPR2 gene promoter region of the traditional Korean group (black) and the westernized Korean group (red), showing a significant difference in the methylation level between the traditional Korean and westernized Korean groups. The identified locations are the same as those marked with an asterisk.

The numerical value confirmed the significance between the traditional Korean food group and the westernized Korean food group at the methylation ratio (mean±SD), p <0.05.

6. Common location verification

The 11 cytosine positions in the NPR2 gene promoter site, where methylation levels are increased by obesity, include 7 cytosine positions (35,791,610 / 35,791,615 / 35,791,625 / 35,791,654 / 35,791,661 / 35,791,667 / 35,791,678) restored by the Korean diet pattern (p < 0.05, Table 12)

The four cytosine positions in the NPR2 gene promoter region, where methylation levels are increased by hypertension, contain three cytosine positions (35,791,654 / 35,791,661 / 35,791,667) restored by the Korean food pattern (p <0.05, Table 13).

Locations in which methylation is commonly found to be changed are the same as those indicated by red squares in FIG.

The numerical value confirmed significance at the level of methylation ratio (mean±SD), p <0.05.

The numerical value confirmed significance at the level of methylation ratio (mean±SD), p <0.05.

Claims (14)

1. A composition for predicting or diagnosing hypertension or obesity, comprising an agent for measuring the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene consisting of the sequence of SEQ ID NO: 1.
2. The method according to claim 1, A primer set capable of amplifying a fragment including the NPR2 gene promoter region consisting of the methylated nucleotide sequence of SEQ ID NO: 1, and hybridizing with the NPR2 gene promoter region consisting of the methylated nucleotide sequence of SEQ ID NO: 1 Probe, methylation specific binding protein capable of binding to the NPR2 gene promoter region consisting of the methylated nucleotide sequence of SEQ ID NO: 1, methylation specific binding antibody or aptamer, sequencing primer, sequencing bi-synthesis primer and sequencing bi-ligation primer One or more compositions selected from the group consisting of.
3. The composition of claim 1, wherein the formulation comprises a primer set consisting of the sequences of SEQ ID NOs: 2 and 3.
4. The composition of claim 1, wherein the methylation site is a cytosine of 257, 264, 266 or 270 in the sequence of SEQ ID NO: 1.
5. The composition of claim 1, wherein the predicted disease is obesity, and the methylation site is a cytosine at position 158, 213, 218, 228, 253, 257, 261, 264, 266, 270 or 281 in the sequence of SEQ ID NO: 1 .
6. A kit for predicting or diagnosing hypertension or obesity comprising the composition of any one of claims 1 to 5.
7. Method of providing information for predicting or diagnosing hypertension or obesity, comprising comparing methylation of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene consisting of the sequence of SEQ ID NO: 1 from the isolated biological sample with the methylation of a normal control sample .
8. The method of claim 7, further comprising detecting methylation of the promoter region of the NPR2 gene from the biological sample.
9. The method of claim 7, wherein the methylation site is a cytosine of 257, 264, 266 or 270 in the sequence of SEQ ID NO: 1.
10. The method of claim 7, wherein the predicted disease is obesity, and the methylation site is a cytosine at position 158, 213, 218, 228, 253, 257, 261, 264, 266, 270 or 281 in the sequence of SEQ ID NO: 1. .
11. The method according to claim 7, wherein when the methylation level obtained from the sample is higher than the methylation level of the normal control sample, it corresponds to hypertension or obesity, or provides information that there is a high possibility of developing.
12. Comparing the methylation level of the promoter region of the NPR2 (Natriuretic Peptide Receptor2) gene consisting of the sequence of SEQ ID NO: 1 in the sample isolated from the individual before and after feeding the subject diet; And

    Selecting a diet for improving obesity or hypertension when the methylation level is reduced after feeding a diet, selecting the diet as a diet for improving obesity or hypertension.
13. The method of claim 12, wherein the methylation site is a cytosine at position 257, 264 or 270 in the sequence of SEQ ID NO: 1.
14. The method of claim 12, wherein the disease of interest is obesity, and the methylation site is a cytosine at position 213, 218, 228, 257, 264, 270 or 281 in the sequence of SEQ ID NO: 1.

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