CN117683873A - Sarcopenia type obesity detection kit and application thereof - Google Patents

Abstract

Compared with other genomics sequencing technologies, the exon sequencing technology only aims at the region of the encoded protein, determines the variation affecting the protein structure, and can effectively reduce the sequencing workload and the sequencing cost. According to the invention, through adopting whole exome sequencing analysis, 1 genetic locus and 5 genes are screened to be associated with SO, and the identified genetic variation is subjected to co-localization and drug target mapping, SO that the relationship between the identified genes and diseases can be deeply identified to a greater extent, the understanding of SO gene structure is expanded, and a foundation is laid for SO treatment, SO prevention, genetics etiology and the like.

Description

Sarcopenia type obesity detection kit and application thereof

Technical Field

The invention relates to the technical field of biological detection, in particular to a sarcopenia type obesity detection kit and application thereof.

Background

Sarcopenia-type obesity (Sarcopenic obesity, SO) is a complex age-related disease characterized by the coexistence of obesity and sarcopenia. SO is associated with an increased risk of poor health outcomes such as cardiovascular disease, disability, and total mortality, as compared to obesity or sarcopenia.

Sarcopenia and obesity are affected by environmental factors, genetic factors, and interactions thereof. Currently, a genome-wide association study (genome-wide association study, GWAS) of Body Mass Index (BMI) and meta-analysis thereof have drawn hundreds of obesity susceptibility gene variation maps, accounting for about 6% of BMI variation, and hundreds of susceptibility gene loci and tens of susceptibility gene loci are found respectively according to the waist-hip ratio and the GWAS of body fat mass adjusted by BMI. The hereditary force of the lean body mass is between 40 and 80 percent, and the genetic force of the holding force is between 30 and 65 percent. While more and more GWAS have identified multiple genetic loci associated with obesity and sarcopenia, genetic variation that can regulate both fat metabolism and skeletal muscle metabolism is still unclear, and thus detection or treatment of sarcopenia-type obesity is lacking.

Disclosure of Invention

In order to solve the technical problems, the invention proves that a single nucleotide polymorphism locus rs1417066 of LYPLAL1-AS1 gene and five genes (MYOZ 3, SLC15A3, RNF130, TNK2 and PDE 3B) are obviously related to susceptibility to sarcopenia type obesity for the first time, and provides a new target point for detection and treatment of the diseases.

A first object of the present invention is to provide a polymorphic molecular marker for detecting a susceptibility to sarcopenia type obesity, the polymorphic molecular marker being one or more of the following:

(1) The rs1417066 locus of the gene LYPLAL1-AS1, wherein the base of the locus is G or A;

(2) 3 single nucleotide polymorphic sites in gene MYOZ 3: rs1324403279 (base G or a); rs778368269 (base a or C); rs1347498035 (base a or G);

(3) 11 single nucleotide polymorphic sites in gene SLC15 A3: rs1856630017 (base a or G); rs767126313 (base a or G); rs1378454033 (base G or C); rs770903289 (base a or AG); rs369072403 (base C or G); rs767414465 (base T or G); 11:60946606 (base G or GC); rs555933857 (base C or CGG); rs1335497946 (base GGAGGC or G); rs1309289714 (base T or G); rs1258207853 (base a or AC);

(4) 2 single nucleotide polymorphism sites in gene RNF 130: rs368728115 (base a or G); rs1356548688 (base C or TCTATGCAG);

(5) 20 single nucleotide polymorphic sites in gene TNK 2: rs920886075 (base C or CACTT); rs532011309 (base a or G); rs201018392 (CG or C base); rs1560111875 (base a or AG); rs541695993 (CG or C base); rs1175665015 (base T or C); rs1007104079 (base a or G); 195862512 (base T or TG); rs1743993432 (base T or TG); rs1275695671 (CG or C base); rs1452249134 (base T or TG); rs1753417424 (base ATCAGC or a); 195883162 (base A or T); 3:1995884979 (base AGGGGCCCCTCCCCTGCT or A); 3:19958849550 (base C or CCCAGGGGCGGG); rs199821504 (base a or G); rs377681378 (base a or G); rs535699406 (base C or CGG); rs199918564 (base GCCCC or G); rs1258919126 (base T or TG);

(6) 18 single nucleotide polymorphic sites in gene PDE 3B: rs1852860313 (base a or ACG); rs758203404 (base TTA or T); rs755065112 (base a or G); rs766545770 (base a or G); rs1456927833 (base G or GC); rs757322376 (base G or a); 11:14819171 (base C or CT); 11:14830697 (base A or G); 11:14830764 (base C or CAG); rs1859862177 (base T or C); 11:14831724 (base AT or a); 11:14832766 (base TA or T); 14832821 (base T or C); rs1255562729 (base AT or a); rs150090666 (base T or C); 14859247 (base G or GT); rs1226269533 (base T or G); rs1848071682 (base A or T).

Further, the genotype-phenotype association is as follows:

(1) In the G/A nucleotide polymorphism of the rs1417066 locus, the base is G which indicates low susceptibility to sarcopenia type obesity and the base is A which indicates high susceptibility to sarcopenia type obesity;

(2) In the gene MYOZ3, rs1324403279 (the base is G or A); rs778368269 (base a or C); the bolded genotype mutation in rs1347498035 (base a or G) 3 single nucleotide polymorphisms indicates high susceptibility to sarcopenia obesity;

(3) In the gene SLC15A3, rs1856630017 (the base is A or G); rs767126313 (base a or G); rs1378454033 (base G or C); rs770903289 (base a or AG); rs369072403 (base C or G); rs767414465 (base T or G); 11:60946606 (base G or GC); rs555933857 (base C or CGG); rs1335497946 (base GGAGGC or G); rs1309289714 (base T or G); the bolded genotype mutation in 11 single nucleotide polymorphisms of rs1258207853 (base a or AC) indicates high susceptibility to sarcopenia obesity;

(4) In gene RNF130, rs368728115 (base a or G); the bolded genotype mutation in rs1356548688 (base C or TCTATGCAG) 2 single nucleotide polymorphisms indicates high susceptibility to sarcopenia-type obesity;

(5) In gene TNK2, rs920886075 (base is C or CACTT); rs532011309 (base a or G); rs201018392 (CG or C base); rs1560111875 (base a or AG); rs541695993 (CG or C base); rs1175665015 (base T or C); rs1007104079 (base a or G); 195862512 (base T or TG); rs1743993432 (base T or TG); rs1275695671 (CG or C base); rs1452249134 (base T or TG); rs1753417424 (base ATCAGC or a); 195883162 (base A or T); 3:1995884979 (base AGGGGCCCCTCCCCTGCT or A); 3:19958849550 (base C or CCCAGGGGCGGG); rs199821504 (base a or G); rs377681378 (base a or G); rs535699406 (base C or CGG); rs199918564 (base GCCCC or G); the bolded genotype mutation in rs1258919126 (base is T or TG) 20 single nucleotide polymorphisms indicates high susceptibility to sarcopenia type obesity;

(6) In the gene PDE3B, rs1852860313 (base A or ACG); rs758203404 (base TTA or T); rs755065112 (base a or G); rs766545770 (base a or G); rs1456927833 (base G or GC); rs757322376 (base G or a); 11:14819171 (base C or CT); 11:14830697 (base A or G); 11:14830764 (base C or CAG); rs1859862177 (base T or C); 11:14831724 (base AT or a); 11:14832766 (base TA or T); 14832821 (base T or C); rs1255562729 (base AT or a); rs150090666 (base T or C); 14859247 (base G or GT); rs1226269533 (base T or G); the bolded genotype mutation in the 18 single nucleotide polymorphisms of rs1848071682 (base a or T) indicates a high susceptibility to sarcopenia-type obesity.

The second object of the invention is to provide an application of a polymorphic molecular marker in preparing a sarcopenia type obesity detection kit for detecting genotypes of one or more of the following genes:

(1) Genotype of rs1417066 locus of gene LYPLAL1-AS 1;

(2) Genotypes of the rs1324403279, rs778368269, and rs1347498035 loci of gene MYOZ 3;

(3) Genotypes of genes SLC15A3, rs1856630017, rs767126313, rs1378454033, rs770903289, rs369072403, rs767414465, 11:60946606, rs555933857, rs1335497946, rs1309289714 and rs 1258207853;

(4) Genotypes rs368728115 and rs1356548688 of gene RNF 130;

(5) Genotypes of genes TNK2, rs920886075, rs532011309, rs201018392, rs1560111875, rs541695993, rs1175665015, rs1007104079, 3:1958629522, rs1743993432, rs1275695671, rs1452249134, rs1753417424, 3:195883162, 3:1995884977, 3:1995884550, rs199821504, rs377681378, rs535699406, rs199918564 and rs 1258919126;

(6) Genotypes of genes PDE3B, rs1852860313, rs758203404, rs755065112, rs766545770, rs1456927833, rs757322376, 11:14819171, 11:14830697, 11:14830764, rs1859862177, 11:14831724, 11:14832766, 11:14832821, rs1255562729, rs150090666, 11:14859247, rs1226269533 and rs 1848071682.

Further, the detection kit comprises one or more of the following primer pairs:

(1) Primer pairs for amplifying the rs1417066 locus of the gene LYPLAL1-AS 1;

(2) A primer pair for amplifying the gene MYOZ 3;

(3) A primer pair that amplifies SLC15 A3;

(4) A primer pair for amplifying RNF 130;

(5) A primer pair for amplifying TNK 2;

(6) Primer pairs for amplifying PDE 3B.

The primer pair is designed aiming at a difference site or a difference gene, can specifically amplify fragments containing corresponding mutation, marks fluorescent dye at the 5' -end of the oligonucleotide primer by a fluorescent marking technology, and one chain of a PCR amplified product carries fluorescent dye of the marked primer. Those skilled in the art will appreciate that specific primer pairs can be synthesized using conventional synthesis techniques.

Further, for ease of identification, the primer pair is provided with an identification label, such as a fluorescent label.

Further, components for PCR amplification and capillary electrophoresis may be included in the detection kit. Such as Taq DNA polymerase, dNTP mixture, mgCl ₂ Solution, PCR reaction buffer and deionized water. The amplified products of the PCR are analyzed for the genotype of the site by capillary electrophoresis separation techniques.

A third object of the present invention is to provide the use of a primer pair in the preparation of a kit for detecting sarcopenia type obesity, the primer pair comprising one or more of the following:

(1) Primer pairs for amplifying the rs1417066 locus of the gene LYPLAL1-AS 1;

(2) A primer pair for amplifying the gene MYOZ 3;

(3) A primer pair that amplifies SLC15 A3;

(4) A primer pair for amplifying RNF 130;

(5) A primer pair for amplifying TNK 2;

(6) Primer pairs for amplifying PDE 3B.

A fourth object of the present invention is to provide a kit for the detection of sarcopenia-type obesity, comprising the following primer pairs for detecting genotypes thereof:

(1) Primer pairs for amplifying the rs1417066 locus of the gene LYPLAL1-AS 1;

(2) A primer pair for amplifying the gene MYOZ 3;

(3) A primer pair that amplifies SLC15 A3;

(4) A primer pair for amplifying RNF 130;

(5) A primer pair for amplifying TNK 2;

(6) Primer pairs for amplifying PDE 3B.

It is a fifth object of the present invention to provide a therapeutic agent for sarcopenia type obesity, which is designed with the rs1417066 locus of gene LYPLAL1-AS1, gene MYOZ3, gene SLC15A3, gene RNF130, gene TNK2 or gene PDE3B AS targets, and which is used for modulating the abnormality of downstream signal pathway or protein due to the above locus or gene mutation.

By means of the scheme, the invention has at least the following advantages:

the invention identifies genetic variation affecting SO based on large-scale exon sequencing data, and provides new insight for the treatment and prevention of SO. Specifically, a specific site and the association between five differential genes and sarcopenia type obesity are found in high throughput screening, and the identified genetic variation is subjected to co-localization and drug target mapping, so that the finding provides a new direction for the detection and treatment of sarcopenia type obesity.

The foregoing description is only an overview of the present invention, and is presented in terms of preferred embodiments of the present invention and the following detailed description of the invention in conjunction with the accompanying drawings.

Drawings

In order that the invention may be more readily understood, a more particular description of the invention will be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings.

FIG. 1 is a Manhattan plot of a sarcopenia type obese single variant associated meta analysis.

FIG. 2 is a Manhattan plot of gene load test meta analysis of sarcopenia obesity.

Detailed Description

The present invention will be further described with reference to the accompanying drawings and specific examples, which are not intended to be limiting, so that those skilled in the art will better understand the invention and practice it.

The scheme of the invention is as follows:

the invention adopts transverse data to analyze depth causal relationship, and comprises the following specific steps:

s1: quality control is carried out on the whole exon sequencing data, and data which do not meet the requirements are removed;

s2: determining diagnosis standards of SO, and defining SO cases and controls;

s3: performing a whole exome single variation association analysis to determine genetic variation associated with the SO;

s4: performing a gene load test on the annotation as a predicted loss of function variation;

s5: performing co-location analysis to calculate co-location posterior probability between the significant signal and the eQTL/pQTL;

s6: the identified genes are mapped to drug targets using a drug target database.

The results were as follows:

1) The invention discovers that one genetic locus (rs 1417066) and 5 genes are related to SO through analyzing the whole exome sequencing data of the British biological sample library. Specifically, specific information on genetic loci and genes is as follows:

2) Through the detection of the pathogenic genes and the mutation conditions thereof, the screening, (auxiliary) diagnosis, detection, monitoring and prediction evaluation of the sarcopenia type obesity are realized.

Example 1

1) Data sources:

both SO cases and controls were selected from a sample of UK Biobank (UK Biobank, UKB) and UKB studies received ethical approval from the ethical committee of the northwest research center (11/NW/0382), with all participants providing informed consent. This study (application number 41542) has been approved by the general ethical authorities of the UKB cohort.

2) Quality control of whole exome sequencing data:

full exome sequencing (WES) data was from 200,643 participants published publicly by UKB. We included only eligible european persons (data field 22006) and deleted participants who self-reported sex inconsistent with genetic sex, sex chromosomes that were aneuploidies or who withdrawn informed consent. Furthermore, we excluded the gene repeat participants identified using the KING software and the genotype deletion rate identified by the PLINK software>10% of participants. For genetic variation, we exclude genotype deletions>10%, hardy-Weinberg equilibrium test P value<1×10 ^-15 And minor allele counts (minor allele count, MAC)<2, and a genetic variation of 2. A total of 167,000 participants and approximately 8,070,899 genetic variations were retained through a series of quality controls.

Furthermore, our previous study incorporated the WES genotype and the whole genome Genotyping (GWAS) genotype of 167,000 UKB european participants into one interpolation reference panel, and then interpolated the WES data for 241,911 UKB participants of homogeneous european populations with only the GWAS genotype. Interpolation accuracy (r) ² ) Remain at a medium to high level throughout all frequency ranges, including very few frequency ranges. For interpolation data we further exclude variations (r ² <0.3). Thus, about 661 ten thousand well-interpolated genetic variations were retained for subsequent analysis. We then used WES data obtained from the UKB as a discovery sample, interpolated data as a validation sample, and then combined the results of the two samples for meta-analysis to identify SO-related genetic variations and genes. The quality control of the interpolated samples is consistent with the found samples.

3) Determining SO diagnostic criteria, defining SO cases and controls:

SO is defined using the recently proposed definitions and diagnostic criteria of the European clinical nutrition and metabolism institute and European obesity research Association. SO is defined as a combination of obesity (measured by high fat mass percentage (fat mass percentage, FM%)) and sarcopenia (measured by low muscle mass and low muscle strength). Specifically, obesity is defined as female FM% >40.7%, male >27.3%. Low muscle mass is defined as appendiceal lean body mass (appendicular lean mass, ALM) after weight adjustment below a critical reference value, i.e. male ALM/body weight <28.27%, female <23.47%. Low muscle strength is defined as a male grip strength <27kg and a female grip strength <16kg. The final samples included 282,164 participants (6,890 SO and 275,274 controls).

4) Performing whole exome monovariant association analysis:

according to the acquisition mode of the exon sequencing data, the sample is split into two independent parts, wherein 116,171 (2,887 cases of SO and 113,284 cases of controls) are found samples, and the exon sequencing data are obtained through sequencing; the remaining 165,993 (4,003 cases SO and 161,990 cases control) were validated samples and their exon sequencing data were obtained by genotype interpolation.

We first performed a monovariant association analysis in the discovery samples using REGENIE v3.2.1 software and identified significant genetic variations using age, sex, height, assessment center and the first 10 genetic principal components as covariates (P<1×10 ^-8 ) The verification is then performed in a verification sample.

When the correlation P value of the verification sample is smaller than 0.05, the correlation direction is consistent with the found sample, and the verification is successful. For sites that were successfully validated, the correlation results of the found samples and validated samples were combined using a fixed-effect inverse variance weighted meta analysis in METAL software.

The prominent site is defined as the most prominent SNP and its flanking 1Mb bi-directional region.

5) Gene load test:

we used Ensembl Variant Effect Predictor (VEP) software for Minor Allele Frequencies (MAF)<Rare variations of 0.01 are annotated. All genetic variations noted stop_gain, stop_lost, start_lost, splice_donor_ variant, splice _receiver_variant and frame shift_variant are defined as prediction loss of functionLoss-of-function (plif) variation. After annotation, a total of 11,625 genes were available for analysis. We established a binary variable for the presence of plofvariation and three gene load models for each gene based on three MAF thresholds (1%, 0.1% and 0.01%). Covariates of the gene load test were identical to the monovariant association analysis. Likewise, nominal significance was achieved in the discovery samples (P<0.05 Verifying in a verification sample, and performing meta analysis on the gene successfully verified. The significance level of the gene-based stress test was set to the threshold P of Bonferroni correction<4.30×10 ^-6 (i.e., 0.05/11625). For a plurality of load models of the same gene, only the load model with the lowest P value is reported. Only genes in the discovery and validation samples were nominally significant (P<0.05 And in the same direction, are defined as significant genes.

6) Other functional analysis:

co-localization analysis: all genetic variations within 500kb of both sides of the most significant variation were extracted and matched to the significant eQTL and pQTL data, and then co-localization posterior probabilities between the significant and QTL signals were calculated using the R software package "coloc".

For identifying genes that are significantly associated with SO, we used Human Protein Atlas (HPA) to query their RNA information in different tissues and single cell types.

Patent drug property analysis: the identified genes are mapped to drugs using a therapeutic drug target database.

Example 2 differential site analysis

In the whole-exome single-variant association analysis, a total of 14 genetic variants were found at the whole-exome significance level (P<1×10 ^-8 ) The above is significantly related to the risk of SO (fig. 1). They are all located at the same locus 1q 41. Of these, the most pronounced genetic variation rs1417066 (P _meta ＝1.75×10 ^-14 ，P _{Discovery samples} ＝2.18×10 ^-9 ，P _{Verification of samples} ＝6.22×10 ^-7 Ratio [ odds ratio, OR ]]1.15,95% confidence interval [ confidence interval, CI]1.11-1.19) are annotated AS introns of LYPLAL1-AS 1. This indicates that the number of the cells in the cell,for rs1417066, individuals carrying effector allele a are 1.15 times more at risk for SO than individuals carrying allele G.

We then used the "coloc" package to conduct a co-localization analysis between the significant site and the eQTL/pQTL. We found that this site may affect expression of the LYPLAL1-AS1 gene in subcutaneous fat, transverse colon, esophageal-gastric-esophageal junction and renal cortex tissue (i.e., PP4> 0.85). In addition, co-localization analysis also demonstrated that this site also affected the expression of the fatty element (ADIPOQ) protein in plasma (table 1).

TABLE 1 Co-location results

Example 3: differential gene analysis

1. Screening of differential genes

FIG. 2 shows a Manhattan plot of gene load testing among 11,625 genes. Meta analysis found 7 genes to be significant under Bonferroni correction threshold (P<0.05/11625＝4.30×10 ^-6 ). Wherein, AC13644.3 (P _{Discovery samples} ＝7.15×10 ^-7 ,P _{Verification of samples} ＝0.57,P _meta ＝9.93×10 ^-9 ) Nominal level significance was not achieved in the validation samples (P<0.05)，SCP2(P _{Discovery samples} ＝0.42,P _{Verification of samples} ＝9.83×10 ^-5 ,P _meta ＝1.66×10 ^-6 ) The nominal level significance was not reached in the found samples, and therefore the two genes were not considered significant. The remaining five genes all reached nominal level significance in the discovery and validation samples. PDE3B (P) _{Discovery samples} ＝3.55×10 ^-2 ,P _{Verification of samples} ＝9.83×10 ^-5 ,P _meta ＝1.10×10 ^-6 )、MYOZ3(P _{Discovery samples} ＝1.93×10 ^-2 ,P _{Verification of samples} ＝7.01×10 ^-4 ,P _meta ＝1.41×10 ^-7 )、SLC15A3(P _{Discovery samples} ＝9.14×10 ^-3 ,P _{Verification of samples} ＝8.68×10 ^-4 ,P _meta ＝6.82×10 ^-7 )、RNF130(P _{Discovery ofSample of} ＝5.54×10 ^-4 ,P _{Verification of samples} ＝3.16×10 ^-2 ,P _meta ＝4.07×10 ^-6 ) And TNK2 (P) _{Discovery samples} ＝5.75×10 ^-4 ,P _{Verification of samples} ＝2.41×10 ^-3 ,P _meta ＝8.75×10 ^-8 ) No report was made on sarcopenia type obesity (Table 2).

TABLE 2 Gene-based load test results

Note that: OR: a dominance ratio; 95% CI: 95% confidence interval of ratio; significant genes are indicated in bold.

2. Biological support of differential genes

To find biological support for the identified genes, we assessed the RNA expression levels of these genes in different tissues and single cell types based on published databases. In general, RNA expression levels of PDE3B genes are tissue-enhanced in adipose tissue and cell-type-enhanced in microglia, astrocytes, inhibitory neurons, excitatory neurons and oligodendrocyte precursor cells. RNA expression levels of the MYOZ3 gene are enriched in skeletal muscle and cell types are enriched in skeletal muscle cells and perivascular cells. The RNA expression levels of SLC15A3 and RNF130 genes were low in tissue specificity and cell type was enhanced in Huo Fubao L cells and Kupffer cells. Finally, the RNA expression level of the TNK2 gene is tissue-enhanced in brain tissue, cell-type-enhanced in oligodendrocyte precursor cells and horizontal cells.

3. Drug target analysis

To query potential drug targets, we cross-reference different drug target databases and annotate identified genes. TTD database shows that PDE3B and TNK2 are targets for patent records and SLC15A3 is a target for literature reporting. Furthermore, the drug class database classification showed that PDE3B and TNK2 genes belong to class 1 (table 3).

TABLE 3 potential drug targets for significant genes

The above results show that the use of several genes found herein as drug targets for sarcopenia-type obesity is not disclosed.

It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations and modifications of the present invention will be apparent to those of ordinary skill in the art in light of the foregoing description. It is not necessary here nor is it exhaustive of all embodiments. And obvious variations or modifications thereof are contemplated as falling within the scope of the present invention.

Claims (10)

1. A polymorphic molecular marker for detecting a susceptibility to sarcopenia type obesity, wherein the polymorphic molecular marker is one or more of the following:

(1) The rs1417066 locus of the gene LYPLAL1-AS1 is G or A;

(2) A gene MYOZ3 comprising 3 single nucleotide polymorphic sites: rs1324403279, the base is G or A; rs778368269, the base is A or C; rs1347498035, the base is A or G;

(3) The gene SLC15A3 comprises 11 single nucleotide polymorphism sites: rs1856630017, the base is A or G; rs767126313, the base is A or G; rs1378454033, the base is G or C; rs770903289, wherein the base is A or AG; rs369072403, the base is C or G; rs767414465, the base is T or G;11:60946606, base G or GC; rs555933857, the base is C or CGG; rs1335497946, wherein the base is GGAGGC or G; rs1309289714, the base is T or G; rs1258207853, the base is A or AC;

(4) Gene RNF130, comprising 2 single nucleotide polymorphism sites: rs368728115, the base is A or G; rs1356548688, the base is C or TCTATGCAG;

(5) Gene TNK2, comprising 20 single nucleotide polymorphic sites: rs920886075, the base is C or CACTT; rs532011309, the base is A or G; rs201018392, wherein the base is CG or C; rs1560111875, wherein the base is A or AG; rs541695993, wherein the base is CG or C; rs1175665015, the base is T or C; rs1007104079, the base is A or G; 3:195862592, the base is T or TG; rs1743993432, the base is T or TG; rs1275695671, wherein the base is CG or C; rs1452249134, the base is T or TG; rs1753417424, wherein the base is ATCAGC or A; 195883162, base A or T; 3:1995884979, base AGGGGCCCCTCCCCTGCT or A; 3:19958849550, base C or CCCAGGGGCGGG; rs199821504, the base is A or G; rs377681378, the base is A or G; rs535699406, the base is C or CGG; rs199918564, base GCCCC or G); rs1258919126, the base is T or TG;

(6) A gene PDE3B comprising 18 single nucleotide polymorphic sites: rs1852860313, wherein the base is A or ACG; rs758203404, wherein the base is TTA or T; rs755065112, the base is A or G; rs766545770, the base is A or G; rs1456927833, the base is G or GC; rs757322376, the base is G or A;11:14819171, base C or CT;11:14830697, base A or G;11:14830764, base C or CAG; rs1859862177, the base is T or C;11:14831724, base AT or a;11:14832766, base is TA or T;11:14832821, base is T or C; rs1255562729, the base is AT or A; rs150090666, the base is T or C;11:14859247, base G or GT; rs1226269533, the base is T or G; rs1848071682, the base is A or T.

2. The polymorphic molecular marker of claim 1, wherein the genotype is associated with the phenotype as follows:

(1) In the G/A nucleotide polymorphism of the rs1417066 locus, the base is G which indicates low susceptibility to sarcopenia type obesity and the base is A which indicates high susceptibility to sarcopenia type obesity;

(2) In the gene MYOZ3, the genotype with the rs1324403279 base of G, rs778368269 base and the A, rs1347498035 base of A indicates that the susceptibility of sarcopenia type obesity is high;

(3) In the gene SLC15A3, the genotype of which the rs1856630017 base is A, rs767126313 base, A, rs1378454033 base, G, rs770903289 base, A, rs369072403 base, C, rs767414465 base, T, 11:60946606 base, G, rs555933857 base, C, rs1335497946 base, GGAGGC and rs1309289714 base, T, rs1258207853 base and A indicates that the susceptibility to sarcopenia type obesity is high;

(4) In the gene RNF130, the genotype with the rs368728115 base of A, rs1356548688 base of C indicates that the susceptibility of sarcopenia type obesity is high;

(5) In the gene TNK2, genotype indicating sarcopenia type obesity with the characteristics of C, rs532011309 base for rs920886075 base for A, rs201018392 base for CG, rs1560111875 base for A, rs541695993 base for CG, rs1175665015 base for T, rs1007104079 base for A, 3:195869522 base for T, rs1743993432 base for T, rs1275695671 base for CG, rs1452249134 base for T, rs1753417424 base for ATCAGC, 3:195883162 base for A, 3:1995884977 base for AGGGGCCCCTCCCCTGCT, 3:1995884950 base for C, rs199821504 base for A, rs377681378 base for A, rs535699406 base for C, rs199918564 base for GCCCC and rs1258919126 base for T is high in susceptibility;

(6) In the gene PDE3B, genotypes of which the rs1852860313 base is A, rs758203404 base is TTA, the rs755065112 base is A, rs766545770 base is A, rs1456927833 base is G, rs757322376 base is G, the 11:14819171 base is C, the 11:14830677 base is A, the 11:14830764 base is C, rs1859862177 base is T, the 11:14831724 base is AT, the 11:14832766 base is TA, the 11:14832821 base is T, rs1255562729 base is AT, the rs150090666 base is T, the 11:14859247 base is G, rs1226269533 base is T, rs1848071682 base is A indicate high susceptibility to sarcopenia type obesity.

3. Use of the polymorphic molecular marker according to claim 1 or 2 for the preparation of a kit for the detection of sarcopenia-type obesity, wherein the detection kit is used for detecting the genotype of the polymorphic molecular marker.

4. The use according to claim 3, wherein the detection kit comprises a primer pair for detecting a polymorphic molecular marker.

5. The use according to claim 4, wherein the primer pair has an identification tag thereon.

6. The use according to claim 4, wherein the detection kit comprises components for PCR amplification and capillary electrophoresis.

7. The use according to claim 6, wherein the components for PCR amplification and capillary electrophoresis comprise Taq DNA polymerase, dNTP mix, mgCl ₂ Solution, PCR reaction buffer and deionized water.

8. Use of primers for amplifying the polymorphic molecular markers of claim 1 in the preparation of a kit for the detection of sarcopenia type obesity.

9. A kit for the detection of sarcopenia type obesity, comprising a primer for amplifying the polymorphic molecular marker according to claim 1 for detecting the genotype thereof.

10. A therapeutic drug for sarcopenia type obesity is characterized in that the therapeutic drug is designed by taking an rs1417066 locus of a gene LYPLAL1-AS1, a gene MYOZ3, a gene SLC15A3, a gene RNF130, a gene TNK2 or a gene PDE3B AS targets.