Application of leptin gene in preparation of products for auxiliary identification of premature delivery of newborns of Han population

Abstract

The invention discloses application of a leptin gene in preparation of a product for auxiliary identification of premature delivery of newborns of Han population, and belongs to the technical field of biomedicine. Risk assessment is carried out on relevance of polymorphism and clinical phenotypes of neonatal leptin genes, leptin receptor genes, irisin precursor FNDC5 genes and vitamin D receptor genes and premature delivery occurrence, risk factors of premature delivery are analyzed by adopting multi-factor logistic regression, and results show that premature delivery occurrence is based on genetic susceptibility. The result caused by the combined action of various exogenous factors shows that the polymorphic site genotype GG of the leptin gene rs7799039 of the neonates of the Han population is related to premature delivery; the age of the mother is increased, and the preplacenta may be a risk factor of premature delivery. The invention provides a new strategy for preventing premature delivery of neonates of Han population.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical technology, in particular to the application of leptin gene in the preparation of products for assisting in identifying the occurrence of preterm birth in Han population. BACKGROUND

[0002] The World Health Organization (WHO) defines preterm birth (PTB) as a baby born within 37 weeks or a baby born within 259 days from the first day of the mother's last menstrual period to delivery. Preterm infants have small gestational age, low body weight, and multiple organ systems that have not developed maturely, which is the main cause of diseases in various systems and neonatal deaths. Studies have shown that the number of deaths due to preterm birth and preterm birth complications accounts for 16% of the total number of deaths of children under 5 years old worldwide, and preterm infants account for 35% of the number of neonatal deaths. Preterm infants will have short-term health problems such as lung disease, low body temperature, feeding difficulties, and infection after birth, as well as long-term respiratory, metabolic, and neurological system problems that can lead to repeated hospitalization for treatment; and can also lead to the occurrence of various adult diseases such as cardiovascular disease and diabetes. Preterm birth not only harms the child itself, but also brings a heavy burden to the family, society, and medical resources as the length of hospitalization increases.

[0003] The etiology and pathogenesis of PTB are still unclear, and can be affected by various factors such as maternal and fetal factors, placenta and its accessory structures. According to the study of twins and their families, genetic factors account for 15%-35% of the risk of preterm birth, and the risk of preterm birth in pregnant women with a history of preterm birth is 15%-50%, which is much higher than the risk of preterm birth in families without a history of preterm birth, so genetic factors play an important role in the occurrence of preterm birth. In a series of prospective studies by Salem et al., the mother's peripheral blood and the newborn's umbilical cord blood were detected, showing that the risk of PTB in mothers carrying the leptin AA genotype was 2.53 times and 2.38 times higher than that in mothers carrying the AG and GG genotypes, respectively; the risk of PTB in newborns carrying the leptin AA genotype was 2.8 times higher than that in newborns carrying the AG genotype. The risk of severe PTB in mothers carrying the leptin receptor AA and AG genotypes was 4.32 and 4.76 times higher than that in mothers carrying the GG genotype. The risk of preterm birth in newborns carrying the FNDC5 GG genotype was increased by 2.124 times, and the risk of preterm birth in mothers carrying the FNDC5 GG genotype was increased by 2.18 times. In the study by Rosenfeld et al., the mother's and newborn's umbilical cord blood were collected; the risk of preterm birth in mothers carrying the ApaI AA genotype was increased by 2 times, and the risk of preterm birth in newborns carrying the BsmI BB genotype was a risk factor.

[0004] Both mother and fetus as a whole of two-way interaction, SNP of both genes will affect the risk of premature birth, genetic variation of newborn also determines the duration of pregnancy of mother, even suggest that the time of pregnancy is affected by genetic variation of newborn greater than the genome of mother. There is no research on the correlation between leptin gene, leptin receptor gene, FNDC5 gene and vitamin D receptor gene of newborn and the occurrence of premature birth in China; Single Nucleotide Polymorphisms (SNPs) have significant racial differences, and different ethnic groups have different genetic susceptibility, and it is particularly important to study the genetic susceptibility of premature birth in Chinese Han newborn population. SUMMARY

[0005] The purpose of the present application is to provide the application of leptin gene in preparing the product for assisting in identifying the occurrence of premature birth of Han newborn, to solve the problems in the prior art, to evaluate the correlation between the polymorphism of leptin gene, leptin receptor gene, FNDC5 gene and vitamin D receptor gene of newborn, clinical phenotype and the occurrence of premature birth, and to screen out GG genotype of rs7799039 polymorphic site of leptin gene as a high risk factor of premature birth of Han newborn, which is significantly related to the premature birth of Han newborn, and the present application provides a new strategy for preventing premature birth of Han newborn.

[0006] To achieve the above purpose, the present application provides the following scheme:

[0007] The present application provides the application of leptin gene in preparing the product for assisting in identifying the occurrence of premature birth of Han newborn, and the genotype of rs7799039 polymorphic site of leptin gene (NCBI gene accession number is NC_000007.14) includes AA, AG and GG.

[0008] Preferably, the GG genotype of the rs7799039 polymorphic site is related to the occurrence of premature birth of Han newborn.

[0009] Preferably, the gestational age of the Han newborn is less than 259 days.

[0010] The present application also provides the application of reagent for detecting the genotype of rs7799039 polymorphic site of leptin gene in preparing the product for assisting in identifying the occurrence of premature birth of Han newborn, and the genotype of rs7799039 polymorphic site includes AA, AG and GG.

[0011] Preferably, the GG genotype of the rs7799039 polymorphic site is related to the occurrence of premature birth of Han newborn.

[0012] Preferably, the gestational age of the Han population newborn is <259 days.

[0013] The application further provides a primer set for detecting the genotype of the polymorphic site rs7799039 of the leptin gene, wherein the primer set comprises a forward primer with the nucleotide sequence shown in SEQ ID NO. 1, a reverse primer with the nucleotide sequence shown in SEQ ID NO. 2, and an extension primer with the nucleotide sequence shown in SEQ ID NO. 3.

[0014] The application further provides application of the primer set in preparation of a kit for assisting in identifying a reagent related to premature birth of a Han population newborn.

[0015] Preferably, the gestational age of the Han population newborn is <259 days.

[0016] The application further provides a kit for detecting the genotype of the polymorphic site rs7799039 of the leptin gene, wherein the kit comprises the primer set.

[0017] The application discloses the following technical effects:

[0018] The application detects SNP typing of the gene sites rs7799039, rs1137101, rs1746661, rs726344, rs2228570, rs1544410, rs7975232 and rs731236 of the newborn. After the mother's age and placenta previa are corrected by logistic regression analysis, the risk of the genotype, allele and genetic mode of each SNP site and the occurrence of premature birth is evaluated, and the risk factors of premature birth are analyzed by multi-factor logistic regression analysis. The results show that: in the rs7799039 site, the A and G allele frequencies of the research group are 65.9% and 31.4% respectively, the A and G allele frequencies of the control group are 75.9% and 24.1% respectively, and the distribution difference has statistical difference (OR: 1.614, 95% CI: 1.044-2.495, P=0.031). After the mother's age and placenta previa are corrected, in the codominant genetic mode, it is found that the risk of premature birth of the GG genotype is significantly increased compared with the AA genotype (OR: 3.105, 95% CI: 1.195-8.063, P=0.020); in the recessive genetic mode, it is found that the risk of premature birth of the GG genotype is significantly increased compared with the A allele (AG+AA) (OR: 3.036, 95% CI: 1.201-7.675, P=0.019); in the additive genetic mode, it is found that the risk of premature birth of the G allele is significantly increased (OR: 1.669, 95% CI: 1.075-2.590, P=0.022). The multi-factor logistic regression analysis shows that the rs7799039 genotype GG, the mother's age and placenta previa are the risk factors of premature birth (P<0.05). Therefore, it is found that the occurrence of premature birth is caused by the joint action of multiple exogenous factors on the basis of genetic susceptibility, the genotype GG of the leptin gene rs7799039 polymorphic site of the newborn of the Han nationality is related to the occurrence of premature birth, and the increase of the mother's age and placenta previa may be the risk factors of premature birth. The application provides a new detection means for the prevention of premature birth. BRIEF DESCRIPTION OF DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed in the embodiments. Obviously, the drawings in the following description only constitute some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained without creative labor.

[0020] Figure 1 Sequenom Basic experimental steps of SNP detection technology

[0021] Figure 2The base sequence graph of the SNP site rs1746661 of the FNDC5 gene of the study group and the control group is shown in the figure; from top to bottom, the genotypes correspond to GG, GT and TT, respectively;

[0022] Figure 3 The base sequence graph of the SNP site rs726344 of the FNDC5 gene of the study group and the control group is shown in the figure; from top to bottom, the genotypes correspond to AG and GT, respectively;

[0023] Figure 4 The base sequence graph of the SNP site rs7799039 of the Leptin gene of the study group and the control group is shown in the figure; from top to bottom, the genotypes correspond to AA, AG and GG, respectively;

[0024] Figure 5 The base sequence graph of the SNP site rs1137101 of the Leptin receptor gene of the study group and the control group is shown in the figure; from top to bottom, the genotypes correspond to AA, AG and GG, respectively;

[0025] Figure 6 The base sequence graph of the SNP site rs2228570 of the FokI gene of the vitamin D receptor of the study group and the control group is shown in the figure; from top to bottom, the genotypes correspond to AA, AG and GG, respectively;

[0026] Figure 7 The base sequence graph of the SNP site rs1544410 of the BsmI gene of the vitamin D receptor of the study group and the control group is shown in the figure; from top to bottom, the genotypes correspond to CC and CT, respectively;

[0027] Figure 8 The base sequence graph of the SNP site rs7975232 of the ApaI gene of the vitamin D receptor of the study group and the control group is shown in the figure; from top to bottom, the genotypes correspond to AA, AC and CC, respectively;

[0028] Figure 9 The base sequence graph of the SNP site rs731236 of the TaqI gene of the vitamin D receptor of the study group and the control group is shown in the figure; from top to bottom, the genotypes correspond to AA and AG, respectively. DETAILED DESCRIPTION

[0029] The various exemplary embodiments of the present application will now be described in detail, which should not be considered as limiting the present application, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present application.

[0030] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. In addition, where a range of values is provided, it is understood that each intervening value, to the upper and lower limit of the range is also specifically disclosed. Each smaller range between any stated value or intervening value in the stated range and any other stated or intervening value in that stated range is encompassed. The upper and lower limits of these smaller ranges can independently be included or excluded in the range.

[0031] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application. All documents mentioned herein are incorporated by reference to disclose and describe in detail the methods and / or materials which are described in them. In the case of conflict between the present specification and any document incorporated herein by reference, the present specification will control.

[0032] Many modifications and variations of the present application described in the specification are possible without departing from the scope or spirit of the application. Other embodiments of the application will be apparent to those skilled in the art from consideration of the specification and practice of the application. The specification and examples are illustrative only.

[0033] As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", "contains", "containing", or variations thereof, are intended to be open-ended terms that mean including, but not limited to.

[0034] Example 1

[0035] 1. Study subjects

[0036] Retrospective analysis of premature infants (107 cases) admitted to the neonatal department of a certain third-grade class-A hospital in Shanghai from January 2019 to November 2020 and full-term infants (108 cases) admitted during the same period. The two groups of newborns were from the Han nationality population in Shanghai and its surrounding areas and had no genetic correlation.

[0037] 1.1 Exclusion criteria

[0038] (1) Newborns with intrauterine growth restriction; (2) Newborns with hemorrhagic diseases; (3) Newborns with connective tissue diseases; (4) Newborns with genetic metabolic diseases; (5) Newborns whose mothers may need to induce labor during pregnancy due to perinatal complications.

[0039] 1.2 Inclusion criteria

[0040] Study group: (1) Gestational age <259 days (37 weeks); (2) No preventive measures and drugs for premature birth were taken before birth: antispasmodics, progesterone, antibiotics.

[0041] Control group: (1) 259 days ≤ gestational age < 294 days (42 weeks); (2) no history of premature birth in the mother.

[0042] 2. Collection of clinical phenotype data

[0043] Basic information of all newborns: gestational age, birth weight, gender; basic information of their mothers: age, number of pregnancies, number of deliveries, mode of delivery, gestational hypertension, gestational diabetes, gestational thyroid dysfunction, gestational anemia; placenta and associated structures of the newborn: amniotic fluid contamination, placenta previa, placental abruption, fetal distress in utero, multiple pregnancy, etc.

[0044] 3. Genotype and genetic mode analysis

[0045] Analysis of candidate SNP sites in the study group and the control group: leptin gene (human leptin gene, LEP) rs7799039; leptin receptor gene (leptin receptor gene, LEPR) rs1137101; FNDC5 gene rs1746661, rs726344; Vitamin D receptor (Vitamin D, VDR) FokI gene rs2228570, BsmI gene rs1544410, ApaI gene rs7975232, TaqI gene rs731236 alleles, genotypes and genetic mode differences. Set A as the high-frequency allele of SNP, B as the low-frequency allele, and compare AB vs. AA and BB vs. AA in the codominant mode with AA genotype as the reference; compare AB+BB vs. AA in the dominant mode with AA genotype as the reference; compare BB vs. AA+AB in the recessive mode with AA+AB combined genotype as the reference; compare AB vs. AA+BB in the overdominant mode with AA+BB combined genotype as the reference; and perform B allele dosage analysis as B alleles increase in order with AA, AB and BB as B alleles in the additive mode. This study was approved by the Ethics Committee of Shanghai Ninth People's Hospital, and the ethics approval number was SH9H-2022-T54-2.

[0046] 4. Research methods

[0047] 4.1 Collection and processing of specimens, DNA extraction and quality detection

[0048] 200 μL of peripheral venous blood from the study group and the control group was collected in an EDTA anticoagulant tube and stored in a -80℃ refrigerator. Ezup column genomic DNA extraction kit (No. B518251) was used to extract whole blood genomic DNA.

[0049] 4.2 Primer design

[0050] The primer software was used to design the primer sequences for PCR amplification and single base extension of 8 candidate SNP sites using Sequenom Genotyping Tools and Massarray Assay Design software, as shown in Table 1.

[0051] Table 1 Primer sequences of SNP sites of leptin gene, leptin receptor gene, FNDC5 gene and vitamin D receptor gene

[0052]

[0053]

[0054] 4.3 Genotyping of SNP sites

[0055] Sequenom SNP detection technology was used for genotyping of SNP sites. Sequenom SNP detection technology combined with multiplex PCR technology, MassARRAY iPLEX single base extension technology and matrix-assisted laser desorption / ionization-time of flight mass spectrometry (MALDI-TOF) for genotyping detection. The basic flow chart is shown in Figure 1 .

[0056] 4.5 Statistical analysis

[0057] SPSS 26.0 software package was used for statistical analysis. Non-normally distributed measurement data were expressed as median (interquartile range) [P50 (P25, P75)], and Mann-Whitney rank sum test was used for comparison between groups; count data were expressed as percentages, and chi-square (x 2 ) test was used for comparison between groups; in genetic mode analysis, logistic regression analysis was used to correct maternal age and placenta previa, and the risk of each gene SNP site and premature birth was evaluated, and the obtained odds ratio and its 95% confidence interval were used to represent the risk intensity.

[0058] 5. Results and analysis

[0059] 5.1 Comparison of clinical phenotype analysis between study group and control group

[0060] According to the inclusion and exclusion criteria, 107 preterm infants were included in the study group, and 108 full-term infants were included in the control group. Compared with the control group, the study group had statistically significant differences in maternal age, maternal gestational hypertension, placenta previa, and multiple pregnancy (z=-3.039, P=0.002; x 2 =15.115, P=0.000; x 2 =6.791, P=0.009; x 2 =17.448, P=0.000) and no statistically significant differences in maternal pregnancy times, birth times, neonatal gender, cesarean section, maternal gestational diabetes, thyroid function abnormalities during pregnancy, anemia during pregnancy, placental abruption, and fetal distress (all P>0.05). Compared with the study group, the control group had a higher incidence of amniotic fluid contamination at birth (x 2 =12.592, P=0.000), as shown in Table 2.

[0061] Table 2 Comparison of clinical phenotypes of neonates and mothers in the study group and the control group

[0062]

[0063]

[0064] 5.2 Base sequence chart of gene sites in the study group and the control group, as shown in Figures 2-9 .

[0065] 5.3 Comparison of five genetic patterns of target gene sites in the study group and the control group

[0066] The gene sites in the application all accord with Hardy-Weinberg equilibrium law (P values are 0.973, 1, 0.190, 1, 0.596, 0.723, 0.597 respectively), and have good population representativeness. The allele distribution frequency of rs7799039 site, the allele frequency of group A is 65.9%, and the allele frequency of group G is 31.4%; the allele frequency of control group A is 75.9%, and the allele frequency of group G is 24.1%, and the difference in allele distribution is statistically different, and the risk of premature birth of carrying G allele is 1.614 times of that of carrying A allele (OR 1.614, 95% CI 1.044-2.495, P=0.031). After correcting the mother's age and placenta previa by logistic regression analysis, the analysis of codominant (GG vs. AA, AG vs. AA) genetic mode shows that, compared with AA genotype, the risk of premature birth of GG genotype is significantly increased (OR 3.105, 95% CI 1.195-8.063, P=0.020), and the genetic susceptibility of AG genotype to premature birth is not related (OR 1.062, 95% CI 0.676-1.957, P=0.848); the analysis of dominant (AG+GG vs. AA) genetic mode shows that, compared with AA genotype, the genetic susceptibility of AG+GG to premature birth is not related (OR 1.397, 95% CI 0.798-2.445, P=0.241); the analysis of recessive (GG vs. AG+AA) genetic mode shows that, compared with A allele (AG+AA), the risk of premature birth of GG genotype is significantly increased (OR 3.036, 95% CI 1.201-7.675, P=0.019); the analysis of superdominant (AG vs. GG+AA) genetic mode shows that, compared with GG+AA combined genotype, the genetic susceptibility of AG genotype to premature birth is not related (OR 0.869, 95% CI 0.481-1.570, P=0.642); the analysis of additive (G allele increasing) genetic mode shows that, the risk of premature birth of G allele increasing is significantly increased (OR 1.669, 95% CI 1.075-2.590, P=0.022), and see table 4.

[0067]

[0068] The allele distribution frequency of rs1746661 site was as follows: the G allele frequency was 80.4% and the T allele frequency was 19.6% in the study group; the G allele frequency was 75.5% and the T allele frequency was 24.5% in the control group, and the difference in allele distribution was not statistically significant (P=0.389). After logistic regression analysis to correct the mother's age and placenta previa, the codominant (GT vs. GG, TT vs. GG), dominant (GT+TT vs. GG), recessive (TT vs. GG+GT), overdominant (GT vs. GG+TT) and additive (T allele increasing) genetic patterns were analyzed, and it was found that the genetic susceptibility of rs1746661 site to premature birth was not related (OR: 0.694, 95% CI: 0.108-2.677, P=0.596; OR: 0.802, 95% CI: 0.441-1.460, P=0.471; OR: 0.780, 95% CI: 0.440-1.385, P=0.397; OR: 0.743, 95% CI: 0.196-2.813, P=0.662; OR: 0.817, 95% CI: 0.454-1.472, P=0.501; OR: 0.724, 95% CI: 0.281-1.865, P=0.503), as shown in Table 5.

[0069]

[0070] The allele distribution frequency of rs2228570 site was as follows: the G allele frequency was 55.1% and the A allele frequency was 44.9% in the study group; the G allele frequency was 55.6% and the A allele frequency was 44.4% in the control group, and the difference in allele distribution was not statistically significant (P=0.836); after logistic regression analysis to correct the mother's age and placenta previa, the codominant (AG vs. GG, AA vs. GG), dominant (AG+AA vs. GG), recessive (AA vs. GG+AG), overdominant (AG vs. GG+AA) and additive (A allele increasing) genetic patterns were analyzed, and it was found that the genetic susceptibility of rs2228570 site to premature birth was not related (OR: 0.951, 95% CI: 0.502-1.800, P=0.878; OR: 0.888, 95% CI: 0.395-1.996, P=0.773; OR: 0.942, 95% CI: 0.515-1.723, P=0.847; OR: 0.950, 95% CI: 0.472-1.913, P=0.887; OR: 0.982, 95% CI: 0.562-1.716, P=0.949; OR: 0.970, 95% CI: 0.630-1.492, P=0.888), as shown in Table 6.

[0071]

[0072] The distribution frequencies of alleles of rs7975232 locus in the two groups were as follows: the frequency of C allele was 76.6% and that of A allele was 23.4% in the study group; the frequency of C allele was 74.5% and that of A allele was 25.5% in the control group, and the difference in the distribution of alleles was not statistically significant (P=0.955). After logistic regression analysis to correct the maternal age and placenta previa, the co-dominant (AC vs. CC, AA vs. CC), dominant (AC+AA vs. CC), recessive (AA vs. CC+AC), over-dominant (AC vs. CC+AA) and additive (increasing A allele) genetic models were analyzed, and it was found that the rs7975232 locus was not related to the genetic susceptibility of premature birth (OR: 0.958, 95% CI: 0.537-1.709, P=0.884; OR: 1.047, 95% CI: 0.278-3.941, P=0.946; OR: 0.967, 95% CI: 0.552-1.695, P=0.908; OR: 1.076, 95% CI: 0.291-3.976, P=0.913; OR: 0.953, 95% CI: 0.540-1.684, P=0.869; OR: 0.979, 95% CI: 0.610-1.572, P=0.930), as shown in Table 7. Among them, there was no AG genotype in the rs726344 study group, no AA genotype in the rs1137101 study group, no TT genotype in the rs1544410 two groups, and no GG genotype in the rs731236 two groups, and the genotype distribution in the two groups was not statistically significantly different (P>0.05).

[0073]

[0074] 5.4 Analysis of risk factors for premature birth

[0075] Multivariate logistic regression analysis showed that the rs7799039 genotype GG, maternal age and placenta previa were risk factors for premature birth (P<0.05), as shown in Table 8.

[0076] Table 8 Analysis of risk factors for premature birth

[0077]

[0078] According to the experimental results, it can be seen that premature birth is the result of multiple factors, and the results of the application show that the mother's age in the research group is greater than that in the control group, and as the mother's gestational age increases, the risk of adverse pregnancy increases; the mother's combined placenta previa in the research group is also a high-risk factor for premature birth, which is consistent with the current domestic and foreign research results, and environmental factors are part of the factors for premature birth.

[0079] In terms of genetic factors, the application found that the rs7799039 gene polymorphism of the newborn is related to the occurrence of premature birth, and the risk of premature birth carrying G allele is 1.614 times higher than that of carrying A allele. In genetic mode analysis, it is found that the risk of premature birth of children carrying GG genotype is 3.105 times that of carrying AA genotype. Analysis of recessive genetic mode shows that the risk of premature birth of children carrying GG genotype is 3.036 times that of carrying AA and AG genotypes. Based on the above conclusion, it is considered that GG genotype is a risk factor for premature birth.

[0080] The above-described embodiments are only preferred modes of the application and do not limit the scope of the application. Without departing from the design spirit of the application, various modifications and improvements to the technical solutions of the application made by those skilled in the art shall fall within the protection scope determined by the claims of the application.

Claims

1. Use of the leptin gene in the preparation of a product for aiding the identification of a product associated with the occurrence of preterm birth in a Han population of newborns, characterized in that, The genotype of the rs7799039 polymorphism site of the leptin gene includes AA, AG and GG.

2. Use according to claim 1, wherein The GG genotype of the rs7799039 polymorphism site is associated with the occurrence of premature birth of a Han Chinese newborn.

3. The use according to claim 1, wherein The gestational age of the Han Chinese newborn is less than 259 days.

4. The use of a reagent for detecting the genotype of the polymorphic site of the leptin gene rs7799039 in the preparation of a product for assisting in identifying the correlation of the occurrence of premature birth of a newborn of the Han population, characterized in that, The genotype of the rs7799039 polymorphism site includes AA, AG and GG.

5. The use according to claim 4, wherein the compound is ###0002### The GG genotype of the rs7799039 polymorphism site is associated with the occurrence of premature birth of a Han Chinese newborn.

6. The use according to claim 4, wherein the compound is ###0002### The gestational age of the Han Chinese newborn is less than 259 days.

7. A primer set for detecting the genotype of the polymorphic site rs7799039 of the leptin gene, characterized by, The primer set includes a forward primer with a nucleotide sequence as shown in SEQ ID NO. 1, a reverse primer with a nucleotide sequence as shown in SEQ ID NO. 2, and an extension primer with a nucleotide sequence as shown in SEQ ID NO.

3.

8. Use of the primer set of claim 7 in the preparation of a kit for assisting in identifying a reagent associated with the occurrence of premature birth of a Han Chinese newborn.

9. Use according to claim 8, wherein the compound is ###0002### The gestational age of the Han Chinese newborn is less than 259 days.

10. A kit for detecting the genotype of the polymorphic site rs7799039 of the leptin gene, characterized by, The kit includes the primer set of claim 7.

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