Differential diagnosis hypertensive disorders in pregnancy based on urine peptidome profiling
Objective. To identify peptide panel allowing to discern different hypertensive disorders in pregnancy. Material and methods. A case-control study was conducted. 64 enrolled women were classified into 4 groups: preeclampsia (PE), chronic hypertension (CAH), PE superimposed on CAH and control. Urine samples derived from each patient were analyzed with liquid chromatography coupled with mass-spectrometry (HPLC-MS/MS). The data obtained were processed using statistical and bioinformatic approaches. Results. For all four groups common typical 36 peptides were identified, which are mainly fragments of collagen (COL1A1;COL3A1, etc.), and one peptide uromodulin (UMOD). For patients with hypertensive disorders (PE, PE superimposed on CAH, CAH) characteristic 34 peptide fragments of collagen (COL1A1;COL3A1, etc.) and alpha-fibrinogen (FGA) were identified. For the group of patients with preeclampsia (PE, PE superimposed on CAH) characteristic panel of 16 peptides were identified: 13-th of which are fragments of the protein alpha-1-antitrypsin (SERPINA1), one peptide is a fragment of alpha-1 chain collagen 1 (COL1A1), 1 – alpha-2-HS-glycoprotein (AHSG), 1 – apolipoprotein A-I (APOA1). Semiquantitative analysis of the data the four groups (PE, PE superimposed on CAH, CAH, the control group) non-parametric tests Kruskal-Wallis and Mann-Whitney test showed the presence of 12 peptides, differentiating at least one pair of groups. Separately, a study was conducted on the peptide profile of urine from a patient with a GAG from the time of diagnosis GAG (32-33 weeks) until delivery (36-37 weeks) in the dynamics. Correlation was established between increased levels of peptides protein SERPINA1(A1AT) and the emergence and increasing severity of PE. Conclusion. In the comparative analysis the panel of 12 peptides which can reliably differentiate hypertensive disorders in pregnant women was formed. Fragments of alpha-1-antitrypsin confirmed their importance as markers of pre-eclampsia suggested by the authors in earlier papers. Demonstrated the dynamics of changes in the peptide profile in the manifestation of clinical signs of PE from the patient to the background of the GAG shows real possibilities of application peptidome urinalysis in clinical practice with the aim of timely diagnosis and predictii PE, including PE superimposed on other hypertensive disorders. Further studies are needed to implement the results in clinical practice.Muminova К.Т., Kononikhin А.S., Khodzhaeva Z.S., Shmakov R.G., Sergeeva V.A., Starodubtseva N.L., Bugrova А.Е., Indeykina М.I., Zakharova N.V., Frankevich V.Е., Nikolaev Е.N., Каn N.Е., Sukhikh G.Т.
Keywords
peptidomics
preeclampsia
hypertensive disorders
mass-spectrometry
References
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Received 08.12.2017
Accepted 22.12.2017
About the Authors
Muminova, Kamilla T., Junior Researcher, 1st Department of Obstetrical Pathology of Pregnancy, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79163737707. E-mail: kamika91@mail.ru
Kononikhin, Alexey S., Ph.D., scientific employee of the Laboratory of Proteomics of Human Reproduction, National Medical Research Center of Obstetrics,
Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79167854781. E-mail: konoleha@yandex.ru
Khodzaeva, Zulfiya S., MD, professor, head of the department. 1-st department of obstetrical pathology of pregnancy, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954380788. E-mail: z_khodzhaeva@oparina4.ru
Shmakov, Roman G., chief physician of National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: r_shmakov@oparina4.ru
Sergeeva, Victoria A., post-graduate student of the Laboratory of Mass Spectrometry of Biomacromolecules, N.M. Emanuel Institute for Biochemical Physics,
Russian Academy of Sciences. 119336, Russia, Moscow, Kosygina str. 4. Tel.: +79163444156. E-mail: vik4192@rambler.ru
Starodubtseva, Natalia L., Candidate of Biological Sciences, Head. Laboratory of Proteomics of Human Reproduction, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79164639867. E-mail: n_starodubtseva@oparina4.ru
Bugrova, Anna E., Ph.D., Senior Researcher, Laboratory of Proteomics of Human Reproduction, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79265626590. E-mail: anna.bugrova@gmail.com
Indeykina, Maria I., Junior Researcher, Laboratory of Mass Spectrometry, Biomacromolecules, N.M. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences. 119336, Russia, Moscow, Kosygina str. 4. E-mail: mariind@yandex.ru
Zakharova, Natalia V., Senior Researcher, Laboratory of Mass Spectrometry, Biomacromolecules, N.M. Emanuel Institute for Biochemical Physics,
Russian Academy of Sciences. 119336, Russia, Moscow, Kosygina str. 4. E-mail: nvzakharova@yandex.ru
Chagovets, Vitaliy V., Ph.D., Senior Researcher, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79265626590. E-mail: vvchagovets@gmail.com
Frankevich, Vladimir E., Ph.D., Department of System Biology, National Medical Research Center of Obstetrics, Gynecology and Perinatology named
after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79152604070. E-mail: v_frankevich@oparina4.ru
Kan, Natalia E., MD, head of obstetric department, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79262208655. E-mail: kan-med@mail.ru
Nikolaev, Evgeniy N., doctor of physical and mathematical sciences, head of Laboratory of mass spectrometry of biomacromolecules, N.M. Emanuel Institute
for Biochemical Physics, Russian Academy of Sciences. 119336, Russia, Moscow, Kosygina str. 4. Tel.: +74991378258. E-mail: ennikolaev@rambler.ru
Sukhikh, Gennady T., MD, Academician of the Russian Academy of Sciences, Professor, Director of National Medical Research Center of Obstetrics,
Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381800. E-mail: g_sukhikh@oparina4.ru
For citations: Muminova К.Т., Kononikhin А.S., Khodzhaeva Z.S., Shmakov R.G., Sergeeva V.A., Starodubtseva N.L., Bugrova А.Е., Indeykina М.I., Zakharova N.V., Frankevich V.Е., Nikolaev Е.N., Каn N.Е., Sukhikh G.Т. Differential diagnosis hypertensive disorders in pregnancy based on urine peptidome profiling. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (8): 66-75. (in Russian)
https://dx.doi.org/10.18565/aig.2018.8.66-75
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