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WO2018133634A1 - Marqueur prédictif précoce du diabète sucré gestationnel et son procédé de détection - Google Patents

Marqueur prédictif précoce du diabète sucré gestationnel et son procédé de détection Download PDF

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Publication number
WO2018133634A1
WO2018133634A1 PCT/CN2017/118903 CN2017118903W WO2018133634A1 WO 2018133634 A1 WO2018133634 A1 WO 2018133634A1 CN 2017118903 W CN2017118903 W CN 2017118903W WO 2018133634 A1 WO2018133634 A1 WO 2018133634A1
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protein
serum
gestational diabetes
complement
proteins
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Chinese (zh)
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沈立明
赵丹青
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Shenzhen University
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Shenzhen University
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • the invention relates to the field of biological detection technology, in particular to an early predictive marker for gestational diabetes and a detection method thereof.
  • GDM Gestational diabetes mellitus
  • gestational diabetes is 24-28 weeks of gestation, determined by a 75g glucose tolerance test (OGTT).
  • OGTT glucose tolerance test
  • clinical practice has shown that during this gestational week, although the symptoms of gestational diabetes and the fetus are improved through active intervention, the health of the patient and the fetus has actually been affected to varying degrees before intervention.
  • there is no simple, reliable and effective method for early diagnosis and diagnosis of the disease in the clinic so it is impossible to conduct early intervention on the patient to avoid adverse effects on the patient.
  • the marker is serum differential protein
  • the serum differential proteins include adipocyte plasma membrane associated protein, antithrombin-III, apolipoprotein A5, apolipoprotein E , C4b binding protein ⁇ chain, coagulation factor 9, coagulation factor 5, coagulation factor 10, coagulation factor 12, complement C1s subcomponent, complement C6, complement C7, complement C8 ⁇ chain, complement C8 ⁇ chain, complement C9, complement factor B, Complement factor H, endoplasmic reticulum, fibrinogen ⁇ chain, galectin-3 binding protein, gelsolin, glyceraldehyde-3-phosphate dehydrogenase, Ig mu chain C region, insulin-like growth factor binding protein 5, m- ⁇ -trypsin inhibitor heavy chain H1, meta- ⁇ -trypsin inhibitor heavy chain H4, myeloperoxidase, pregnancy zone protein, protein disulfide isomerase, proteoglycan 4, Several of prothrombin, serum para
  • the early predictive marker of gestational diabetes wherein the serum differential protein comprises three or more different proteins.
  • the early predictive marker of gestational diabetes wherein the serum differential protein is a fat cell plasma membrane associated protein, antithrombin-III, apolipoprotein A5, apolipoprotein E, C4b binding protein ⁇ chain and coagulation Factor 9.
  • the early predictive marker of gestational diabetes wherein the serum differential proteins are adipocyte plasma membrane associated proteins, antithrombin-III and apolipoprotein A5.
  • a method for detecting an early predictive marker for gestational diabetes wherein a change in the concentration of each protein in a serum differential protein of a target to be tested is detected.
  • the method for detecting an early predictive marker of gestational diabetes mellitus, wherein the method for detecting a change in the concentration of each protein in a serum differential protein is one of a high-throughput proteomics method, an enzyme-linked immunosorbent assay, and a protein chip technique. Or several.
  • the early predictive marker of gestational diabetes mellitus of the present invention is serum differential protein, and the change of the serum differential protein concentration is detected by high-throughput proteomics method, enzyme-linked immunosorbent assay or protein chip technology, and further
  • the target pregnancy is 12-16 weeks, whether it will predict gestational diabetes at 24-28 weeks of gestation, the marker has high prediction accuracy, and the detection method is simple and can help potential patients with gestational diabetes.
  • Early diagnosis to avoid adverse effects on the patient and its fetal health.
  • the present invention provides an early predictive marker for gestational diabetes mellitus and a method for detecting the same, and the present invention will be further described in detail below in order to clarify the purpose, technical solutions and effects of the present invention. It is understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
  • the present invention provides an early predictive marker for gestational diabetes, wherein the marker is serum differential protein, and the serum differential proteins include adipocyte plasma membrane-associated protein, antithrombin-III, apolipoprotein A5, Apolipoprotein E, C4b binding protein ⁇ chain, coagulation factor 9, coagulation factor 5, coagulation factor 10, coagulation factor 12, complement C1s subcomponent, complement C6, complement C7, complement C8 beta chain, complement C8 gamma chain, complement C9, Complement factor B, complement factor H, endoplasmic reticulum, fibrinogen ⁇ chain, galectin-3 binding protein, gelsolin, glyceraldehyde-3-phosphate dehydrogenase, Ig mu chain C region, insulin-like Growth factor binding protein 5, meta- ⁇ -trypsin inhibitor heavy chain H1, meta- ⁇ -trypsin inhibitor heavy chain H4, myeloperoxidase, pregnancy zone protein, protein disulfide isomerase, protein Several of glycan 4, prothro
  • the differential protein refers to a differential protein in serum between gestational diabetes patients and healthy pregnant women at 12-16 weeks of gestation.
  • the differential protein first, collect serum samples from at least 500 pregnant women at 12-16 weeks of gestation, and then perform aseptic storage after labeling; after that, at least 500 pregnant women at the time of gestational time reach 24-28 weeks, Having gestational diabetes mellitus for glucose tolerance test, according to clinical criteria to confirm whether there is diabetes, and to find the serum samples of pregnant women and healthy pregnant women diagnosed at 12-16 weeks of pregnancy, group, test, Differential proteins in serum samples from gestational diabetes patients and healthy pregnant women at 12-16 weeks of gestation were obtained as markers for early pregnancy (12-16 weeks) of gestational diabetes.
  • the healthy pregnant woman refers to a pregnant woman who has not been diagnosed with gestational diabetes when the gestation time reaches 24-28 weeks; the gestational diabetes patient refers to the gestation time reaches 24-28 weeks. , pregnant women diagnosed with gestational diabetes.
  • the serum differential protein refers to a protein having a different concentration in serum samples from gestational diabetes patients and healthy pregnant women at 12-16 weeks.
  • the early predictive marker of gestational diabetes mellitus may be all or some of the above 33 proteins.
  • the serum differential protein as a predictive marker may be three or more of the above 33 proteins, and three or more of the above proteins may be used for 12-16 weeks of the target pregnancy.
  • the serum differential proteins as predictive markers are adipocyte plasma membrane associated proteins, antithrombin-III and apolipoprotein A5, early prediction of the three proteins of gestational diabetes
  • the accuracy rate is more than 55%; more preferably, the serum differential proteins as predictive markers are adipocyte plasma membrane-associated protein, antithrombin-III, apolipoprotein A5, apolipoprotein E, C4b binding protein ⁇ chain And coagulation factor 9, the early prediction accuracy of the six proteins for gestational diabetes reached more than 75%.
  • the present invention also provides a method for detecting an early predictive marker of gestational diabetes, wherein a serum differential protein of a target to be tested is detected.
  • concentration change refers to the up-regulation and down-regulation of the expression of each protein; further, the up-regulation refers to the concentration of the protein in the serum of gestational diabetes patients for the same protein at a gestation time of 12-16 weeks.
  • concentration of the protein in the serum of the pregnant woman is more than 1.5 times; the down-regulation refers to the concentration of the protein in the serum of the pregnant woman with a concentration of 1.5 in the serum of the pregnant woman with a pregnancy time of 12-16 weeks. More than double.
  • the change of the serum differential protein concentration in the serum is detected.
  • the method can accurately detect the change of the serum differential protein concentration in the serum of the target pregnancy time of 12-16 weeks, and the detection method is simple and accurate, and can not only greatly facilitate clinical application, but also a broader survey. Screening and early intervention for gestational diabetes provide a basis for avoiding adverse pregnancy outcomes such as pre-eclampsia, macrosomia, fetal malformation, perinatal death, and postpartum type 2 diabetes in pregnant women.
  • the concentration difference of the serum differential protein can be detected by one or two of high-throughput proteomics, enzyme-linked immunosorbent assay or protein chip technology.
  • the two methods are used to separately distinguish the serum differential proteins.
  • the concentration changes are detected, and the test results are compared and analyzed to improve the accuracy of the test results.
  • Serum samples of target 1 with a gestation time of 12-16 weeks were collected, and high-throughput proteomics and enzyme-linked immunosorbent assay were used to compare the serum of serum of pregnant patients with healthy controls.
  • the results showed that compared with the serum of healthy pregnant women, 33 serum differential proteins were obtained in the serum of gestational diabetes patients, 14 of which were up-regulated and 19 were down-regulated, as shown in Table 1 below.
  • Serum samples of target 2 with gestation time of 12-16 weeks were collected, and high-throughput proteomics method was used to compare serum of serum of pregnant patients with healthy controls. The results showed that compared with the serum of healthy pregnant women, 3 serum differential proteins were obtained in the serum of gestational diabetes patients, 2 of which were up-regulated and 1 was down-regulated, as shown in Table 2 below.
  • Serum samples of target 3 with a gestation time of 12-16 weeks were collected, and serum and healthy control sera of gestational diabetes patients were compared by enzyme-linked immunosorbent assay and protein chip technique. The results showed that compared with the serum of healthy pregnant women, 4 serum differential proteins were obtained in the serum of gestational diabetes patients, 2 of which were up-regulated and 2 were down-regulated, as shown in Table 3 below.
  • Serum samples of target 4 with gestation time of 12-16 weeks were collected, and high-throughput proteomics method was used to compare serum of serum of pregnant patients with healthy controls. The results showed that compared with the serum of healthy pregnant women, 5 serum differential proteins were obtained in the serum of gestational diabetes patients, 3 of which were up-regulated and 2 were down-regulated, as shown in Table 4 below.
  • Serum samples of target 5 with a gestation time of 12-16 weeks were collected, and high-throughput proteomics and protein chip techniques were used to compare serum and healthy control sera of gestational diabetes patients.
  • the results showed that compared with the serum of healthy pregnant women, 6 serum differential proteins were obtained in the serum of gestational diabetes patients, of which 0 expressed proteins were up-regulated and 6 expressed proteins were down-regulated, as shown in Table 5 below.
  • Serum samples of target 6 with a gestation time of 12-16 weeks were collected, and high-throughput proteomics method was used to compare the serum of gestational diabetes patients with healthy control sera. The results showed that compared with the serum of healthy pregnant women, 7 serum differential proteins were obtained in the serum of gestational diabetes patients, 4 of which were up-regulated and 3 were down-regulated, as shown in Table 6 below.
  • Serum samples of target 7 with a gestation time of 12-16 weeks were collected, and high-throughput proteomics and enzyme-linked immunosorbent assay were used to compare the serum of serum of pregnant patients with healthy controls.
  • the results showed that compared with the serum of healthy pregnant women, 8 serum differential proteins were obtained in the serum of gestational diabetes patients, 3 of which were up-regulated and 5 were down-regulated, as shown in Table 7 below.
  • Serum samples of target 8 with a gestation time of 12-16 weeks were collected, and serum and healthy control serum of gestational diabetes patients were compared by enzyme-linked immunosorbent assay and protein chip technique. The results showed that compared with the serum of healthy pregnant women, 6 serum differential proteins were obtained in the serum of gestational diabetes patients, 4 of which were up-regulated and 2 were down-regulated, as shown in Table 8 below.
  • Serum samples of target 9 with a gestation time of 12-16 weeks were collected.
  • High-throughput proteomics, enzyme-linked immunosorbent assay and protein chip technique were used to compare the serum of pregnant diabetic patients with healthy control serum. The results showed that compared with the serum of healthy pregnant women, 10 serum differential proteins were obtained in the serum of gestational diabetes patients, 7 of which were up-regulated and 3 were down-regulated, as shown in Table 9 below.
  • Serum samples of target 10 with a gestation time of 12-16 weeks were collected, and high-throughput proteomics method was used to compare the serum of gestational diabetes patients with healthy control sera. The results showed that compared with the serum of healthy pregnant women, 15 serum differential proteins were obtained in the serum of gestational diabetes patients, 7 of which were up-regulated and 8 were down-regulated, as shown in Table 10 below.
  • Serum samples of target 11 with a gestation time of 12-16 weeks were collected, and high-throughput proteomics and protein chip techniques were used to compare serum and healthy control sera of gestational diabetes patients.
  • the results showed that compared with the serum of healthy pregnant women, 20 serum differential proteins were obtained in the serum of gestational diabetes patients, of which 6 expressed proteins were up-regulated and 14 expressed proteins were down-regulated, as shown in Table 11 below.
  • Serum samples of target 12 with a gestation time of 12-16 weeks were collected, and serum and healthy control sera of gestational diabetes patients were compared by protein chip technique. The results showed that compared with the serum of healthy pregnant women, 25 serum differential proteins were obtained in the serum of gestational diabetes patients, 8 of which were up-regulated and 17 were down-regulated, as shown in Table 12 below.
  • Serum samples of target 13 with a gestation time of 12-16 weeks were collected, and serum and healthy control sera of gestational diabetes patients were compared by enzyme-linked immunosorbent assay. The results showed that compared with the serum of healthy pregnant women, 30 serum differential proteins were obtained in the serum of gestational diabetes patients, 11 of which were up-regulated and 19 were down-regulated, as shown in Table 13 below.
  • the present invention provides an early predictive marker for gestational diabetes mellitus and a detection method thereof, wherein the marker is a serum differential protein, using a high-throughput proteomics method, an enzyme-linked immunosorbent assay or a protein chip technique.
  • the concentration of serum differential proteins in early predictors of gestational diabetes mellitus including fatty cell plasma membrane associated proteins, antithrombin-III, apolipoprotein A5, apolipoprotein 33 kinds of proteins such as E; can determine whether the gestational diabetes mellitus will be diagnosed at the 24-28 weeks of gestation by determining the change of the concentration of the serum differential protein detected.
  • the early prediction accuracy of gestational diabetes mellitus is high, and the detection method is simple to operate, which can help potential patients with gestational diabetes to diagnose early and avoid adverse effects on the patient and its fetal health.

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Abstract

L'invention concerne un marqueur prédictif précoce du diabète sucré gestationnel et son procédé de détection, le marqueur étant une protéine sérique spécifique, pouvant correspondre à 33 protéines, par exemple les protéines associées à la membrane plasmique des adipocytes, l'antithrombine-III, l'apolipoprotéine A5 et l'apolipoprotéine E. La mesure du changement de concentration de la protéine sérique spécifique est effectuée par le procédé protéomique à haut débit, par la technique du dosage immuno-enzymatique, ou par une ou plusieurs des techniques de puce à protéines, cela étant suivi, au plus tard lors des 12e à 16e semaines de grossesse, de la prédiction, pour le sujet faisant l'objet de la détection, du risque de souffrir d'un diabète sucré gestationnel à partir des 24e à 28e semaines de grossesse. Le marqueur présente une grande précision prédictive, et le procédé de détection est simple à utiliser et peut aider des patientes à risque de diabète sucré gestationnel à obtenir un diagnostic précoce et à éviter les effets néfastes de la maladie sur leur propre santé et celle de leur fœtus.
PCT/CN2017/118903 2017-01-19 2017-12-27 Marqueur prédictif précoce du diabète sucré gestationnel et son procédé de détection Ceased WO2018133634A1 (fr)

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CN110387414A (zh) * 2019-07-19 2019-10-29 广州市达瑞生物技术股份有限公司 一种利用外周血游离dna预测妊娠期糖尿病的模型
CN112946303A (zh) * 2021-02-23 2021-06-11 江苏省中医院 Tag54:2-fa18:1及其组合物在糖尿病、糖尿病肾病诊断方面的应用
CN116735880A (zh) * 2023-06-15 2023-09-12 郑州大学 用于食管鳞癌早期筛查和诊断的血清蛋白标志物及应用

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CN106706928A (zh) * 2017-01-19 2017-05-24 深圳大学 一种妊娠期糖尿病的早期预测标志物及其检测方法
CN110305970B (zh) * 2019-07-19 2022-10-04 广州市达瑞生物技术股份有限公司 一种基于外周血游离dna检测的巨大儿预测模型
CN112881689B (zh) * 2019-11-29 2023-02-10 张曼 尿液凝血因子ix蛋白及其多肽片段在正常妊娠或妊娠糖尿病中的应用
CN112924682B (zh) * 2019-12-05 2023-02-10 张曼 尿液纤维蛋白原α链蛋白及其多肽片段在正常妊娠中的应用
CN113092773A (zh) * 2019-12-23 2021-07-09 首都医科大学附属北京世纪坛医院 尿液α-胰蛋白酶抑制剂重链H4及其多肽片段在过敏性疾病中的应用
CN114487428A (zh) * 2020-11-12 2022-05-13 首都医科大学附属北京世纪坛医院 尿液补体c3蛋白及其多肽片段在妊娠糖尿病及新生儿评价中的应用
CN114034781A (zh) * 2021-09-16 2022-02-11 中日友好医院 用于孕早期预测妊娠期糖尿病的生物标记物、方法和预警模型

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110387414A (zh) * 2019-07-19 2019-10-29 广州市达瑞生物技术股份有限公司 一种利用外周血游离dna预测妊娠期糖尿病的模型
CN110387414B (zh) * 2019-07-19 2022-09-30 广州市达瑞生物技术股份有限公司 一种利用外周血游离dna预测妊娠期糖尿病的模型
CN112946303A (zh) * 2021-02-23 2021-06-11 江苏省中医院 Tag54:2-fa18:1及其组合物在糖尿病、糖尿病肾病诊断方面的应用
CN112946303B (zh) * 2021-02-23 2023-10-20 江苏省中医院 Tag54:2-fa18:1及其组合物在糖尿病、糖尿病肾病诊断方面的应用
CN116735880A (zh) * 2023-06-15 2023-09-12 郑州大学 用于食管鳞癌早期筛查和诊断的血清蛋白标志物及应用

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