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Obstetrics and Gynegology2023№3
Analysis of HLA class I...

Analysis of HLA class I gene (G) polymorphic alleles in pregnant women in the North-West Region of the Russian Federation

DOI
https://dx.doi.org/10.18565/aig.2022.270

Shengelia M.O., Bespalova O.N., Ivashchenko T.E., Frank N.I., Sultanov I.Yu., Nasykhova Yu.A., Glotov A.S.

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, Saint Petersburg, Russia
Background: The HLA class I system controls the interaction of all immunocompetent cells of the body and determines the recognition of its own and foreign (including altered own) cells, by triggering and realizing an immune response: during the implantation process, in the transplantation of foreign organs and tissues, in autoimmune diseases, and in the development of cancers. Thus, the data available in the world and Russian literature have demonstrated the ability of protein products of HLA-G gene expression to modulate the proliferation of immune system cells, as well as the strength and specificity of the immune response.
Objective: To conduct a molecular biological study of nine HLA-G gene polymorphic alleles in the group of pregnant women in the first trimester and in the population of the North-West Region of the Russian Federation and to identify the relationship to their family obstetric history.
Materials and methods. In 2019 to 2022, the D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology (Saint Petersburg) examined DNA samples from 180 dwellers in the North-West Region of the Russian Federation. Group 1 consisted of 33 pregnant women with reproductive disorders (one or more miscarriages, non-developing pregnancy, ART failures); Group 2 (control) included 29 pregnant women without their family obstetric history; a comparison group comprised 118 people from the population of the North-West Region of the Russian Federation, in which the investigators carried out an associative analysis of HLA-G gene polymorphic alleles (725*C/G, 3741*ins/del 14 bp) and HLA-G*01 alleles (01, G*01:02, G*01:03, G*01:04, G*01:05N, G*01:06 and G*01:07).
Results: The analysis of 3741*ins/del 14 bp polymorphism showed that the Del/Del genotype frequency was 13/33 (39.40%) in pregnant women with a history of reproductive losses, 5/29 (17.24%) in the control group; p = 0.052), and the allele Ins was detected 1,4 times more often in the group without a family obstetric history (20/33 (60.6%) and 24/29 (82.8%), respectively; p=0.056). According to the calculated odds ratio, the carriers of the combined Del/Del and C/C genotype were detected 9 times more frequently among patients with a history of reproductive losses compared to the controls (OR=8.96, CI 1.05;76.74). In Group 1, the HLA-G*01:05N allele was noted to be detected 3.5 times more often than in the population sample.
Conclusion: The findings may judge an association between HLA-G gene alleles and a family obstetric history and may be important in assessing the risk of early reproductive losses and in developing new prevention and treatment strategies for this pregnancy complication.

Authors’ contributions: Bespalova O.N., Ivashchenko T.E. – concept and design of the investigation; Shengelia M.O., Frank N.I., Sultanov I.Yu. – material collection and processing; Shengelia M.O. – statistical data processing; Bespalova O.N., Shengelia M.O. – writing the text; Bespalova O.N., Nasykhova Yu.A., Glotov A.S. – editing.
Conflicts of interest: The authors declare that they have no conflict of interest.
Funding: The article has been prepared for publication within the framework of State Assignment No. АААА-А20-120041390025-9 “Development of diagnostic criteria for predicting early reproductive losses based on the expression of major histocompatibility complex class I antigens G, E, C” of the Ministry of Science and Higher Education of the Russian Federation.
Ethical Approval: The investigation has been approved by the Local Ethics Committee, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology.
Patient Consent for Publication: Voluntary informed consent was obtained from each of the participants included in the investigation.
Authors’ Data Sharing Statement: The data supporting the conclusions of this investigation are available upon request from the corresponding author after approval by the principal investigator.
For citation: Shengelia M.O., Bespalova O.N., Ivashchenko T.E., Frank N.I., Sultanov I.Yu., Nasykhova Yu.A., Glotov A.S. Analysis of HLA class I gene (G) polymorphic alleles in pregnant women in the North-West Region of the Russian Federation.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (3): 99-108 (in Russian)
https://dx.doi.org/10.18565/aig.2022.270

Keywords

HLA-G gene
population of the North-West region of the Russian Federation
spontaneous miscarriage
reproductive losses
Full text (in Russian)

References

  1. Moffett A., Chazara O., Colucci F. Maternal allo-recognition of the fetus. Fertil. Steril. 2017; 107(6): 1269-72. https://dx.doi.org/10.1016/j.fertnstert.2017.05.001.
  2. Djurisic S., Hviid T.V. HLA cass Ib molecules and immune cells in pregnancy and preeclampsia. Front. Immunol. 2014; 5: 652. https://dx.doi.org/10.3389/fimmu.2014.00652.
  3. Баклейчева М.О., Беспалова О.Н., Иващенко Т.Э. Роль экспрессии HLA I класса (G, E и C) в ранних репродуктивных потерях. Акушерство и гинекология. 2020; 2: 30-6. [Bakleicheva M.O., Bespalova O.N., Ivashchenko T.E. Role of class I HLA (G, E, and C) expression in early reproductive losses. Obstetrics and Gynecology. 2020; (2): 30-6. (in Russian)].https://dx.doi.org/10.18565/aig.2020.2.30-36.
  4. Nilsson L.L., Djurisic S., Hviid T.V.F. Controlling the immunological crosstalk during conception and pregnancy: HLA-G in reproduction. Front. Immunol. 2014; 5: 198. https://dx.doi.org/10.3389/fimmu.2014.00198.
  5. Nilsson L.L., Scheike T., Langkilde C.H., Jørgensen N., Hornstrup M.B., Perin T.L. et al. Examining extended human leukocyte antigen-G and HLA-F haplotypes: the HLA-G UTR-4 haplotype is associated with shorter time to pregnancy in an infertility treatment setting when both female and male partners are carriers. Fertil. Steril. 2020; 114(3): 628-39. https://dx.doi.org/10.1016/j.fertnstert.2020.04.052.
  6. Persson G., Melsted W.N., Nilsson L.L., Hviid T.V.F. HLA class Ib in pregnancy and pregnancy-related disorders. Immunogenetics. 2017; 69(8-9): 581-95. https://dx.doi.org/10.1007/s00251-017-0988-4.
  7. Dahl M., Djurisic S., Hviid T.V. The many faces of human leukocyte antigen-G: relevance to the fate of pregnancy. J. Immunol. Res. 2014; 2014: 591489.https://dx.doi.org/10.1155/2014/591489.
  8. Gregori S., Amodio G., Quattrone F., Panina-Bordignon P. HLA-G Orchestrates the early interaction of human trophoblasts with the maternal niche. Front. Immunol. 2015; 6: 128. https://dx.doi.org/10.3389/fimmu.2015.00128.
  9. Сидельникова В.М. Привычная потеря беременности. М.: Триада-Х; 2005. 304c. [Sidelnikova V.M. Habitual pregnancy loss. Moscow: Triada-X; 2005. 304p. (in Russian)].
  10. Иващенко Т.Э., Швед Н.Ю., Беспалова О.H., Тарасенко О.А., Малышева О.В., Демин Г.С., Баранов В.С. Генетические основы предрасположенности к акушерской и гинекологической патологии. Молекулярная медицина. 2007; 3: 19-26. [Ivashchenkо Т.Е., Shved N.Yu., Bespalova O.N., Tarasenko O.A., Malysheva O.V., Dentin G.S., Baranov V.S. Genetic bases of predisposition to obstetric and gynecological diseases. Molecular Medicine. 2007; (3): 19-26. (in Russian)].
  11. Майборода А.А. Генетический полиморфизм: теория и практика. Сибирский медицинский журнал (Иркутск). 2014; 8: 125-9. [Majboroda A.A. Genetic polymorphism: theory and practice. Siberian Medical Journal (Irkutsk). 2014; (8): 125-9. (in Russian)].
  12. Киселева А.Н., Бутина Е.В., Исаева Н.В., Зайцева Г.А., Поздеев Н.М., Овчинников В.В. Характер распределения антигенов системы HLA у супружеских пар с репродуктивными расстройствами. Акушерство, гинекология и репродукция. 2019; 13(2): 111-8. [Kisileva A.N., Butina E.V., Isaeva N.V., Zaitseva G.A., Pozdeev N.M., Ovchinnikov V.V. Distribution of antigens of the HLA-system in married couples with reproductive disorders. Obsterics, Gynecology and Reproduction. 2019; 13(2): 111-8. (in Russian)].
  13. Гордеева Л.А., Воронина Е.Н., Поленок Е.Г., Мун С.А., Нерсесян С.Л., Оленникова Р.В., Филипенко М.Л., Глушков А.Н. Изучение связи полиморфизма гена HLA-G, внутриматочной инфекции и невынашивания беременности у женщин. Медицинская иммунология. 2021; 23(2): 369-80. [Gordeeva L.A., Voronina E.N., Polenok E.G., Mun S.A., Nersesyan S.L., Olennikova R.V., Filipenko M.L., Glushkov A.N. Stude of relationships between HLA-G gene polymorphism, intrauterine infection and reccurent miscarriage in women. Medical Immunology. 2021; 23(2): 369-80. (in Russian)].
  14. Hviid T.V., Hylenius S., Rorbye C., Nielsen L.G. HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels. Immunogenetics. 2003; 55(2): 63-79. https://dx.doi.org/10.1007/s00251-003-0547-z.
  15. Hviid T.V., Rizzo R., Christiansen O.B., Melchiorri L., Lindhard A., Baricordi O.R. HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms. Immunogenetics. 2004; 56(3): 135-41. https://dx.doi.org/10.1007/s00251-004-0673-2.
  16. Nardi Fda S., Slowik R., Michelon T., Manvailer L.F., Wagner B.,Neumann J. et al. High amounts of total and extracellular vesicle derived soluble HLA-G are associated with HLA-G 14-bp deletion variant in women with embryo implantation failure. Am. J. Reprod. Immunol. 2016; 75(6): 661-71. https://dx.doi.org/10.1111/aji.12507.
  17. Lashley L.E., van der Westerlaken L.A., Haasnoot G.W., Drabbels J.J., Spruyt-Gerritse M.J., Scherjon S.A. et al. Maternal HLA-C2 and 14 bp insertion in HLA-G is associated with recurrent implantation failure after in vitro fertilization treatment. Tissue Antigens. 2014; 84(6): 536-44.https://dx.doi.org/10.1111/tan.12452.
  18. Enghelabifar M., Allafan S., Khayatzadeh J., Shahrokh Abadi K., Hasanzadeh Nazarabadi M., Moradi F. et al. Association of the maternal 14-bp insertion/deletion polymorphism in the histocompatibility leukocyte antigen G gene with recurrent implantation failure. Iran. J. Reprod. Med. 2014; 12(9): 641-6.
  19. Rousseau P., Le Discorde M., Mouillot G., Marcou C., Carosella E.D., Moreau P. The 14 bp deletion-insertion polymorphism in the 3' UT region of the HLA-G gene influences HLA-G mRNA stability. Hum. Immunol. 2003; 64(11):1005-10. https://dx.doi.org/10.1016/j.humimm.2003.08.347.
  20. Naghavian E., Abediankenari S., Rahmani Z., Nazari Z., Chabaki M., Alizadeh A. et al. Association of HLA-G null allele polymorphism in women with threatened abortion in comparison with control. J. Mazandaran. Univ. Med. Sci. 2014; 24: 2-7.
  21. Arjmand F., Ghasemi N., Mirghanizadeh S.A., Samadi M. The balance of the immune system between HLA-G and NK cells in unexplained recurrent spontaneous abortion and polymorphisms analysis. Immunol. Res. 2016; 64(3): 785-90. https://dx.doi.org/10.1007/s12026-015-8771-9.
  22. Ober C., Billstrand C., Kuldanek S., Tan Z. The miscarriage-associatedHLA-G -725G allele influences transcription rates in JEG-3 cells. Hum. Reprod. 2006; 21(7): 1743-8. https://dx.doi.org/10.1093/humrep/del036.
  23. Moreau P., Mouillot G., Rousseau P., Marcou C., Dausset J., Carosella E.D. HLA-G gene repression is reversed by demethylation. Proc. Natl. Acad. Sci. USA. 2003; 100(3): 1191-6. https://dx.doi.org/10.1073/pnas.0337539100.
  24. Ober C., Aldrich C.L., Chervoneva I., Billstrand C., Rahimov F., Gray H.L., Hyslop T. Variation in the HLA-G promoter region influences miscarriage rates. Am. J. Hum. Genet. 2003; 72(6): 1425-35. https://dx.doi.org/10.1086/375501.
  25. Donadi E.A., Castelli E.C., Arnaiz-Villena A., Roger M., Rey D., Moreau P. Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association. Cell. Mol. Life Sci. 2011; 68(3): 369-95. https://dx.doi.org/10.1007/s00018-010-0580-7.
  26. Аленичев А.С., Насыхова Ю.А., Иващенко Е.Э., Баранов В.С. Характеристика генетической структуры популяции Северо-Западного региона РФ по гену HLA-G. Экологическая генетика. 2014; 12(2): 74-80. [Alenichev A.S., Nasykhova Y.A., Ivashchenko T.E., Baranov V.S. Population genetic structure for gene HLA-G in Northwest Russia. Russian Journal of Genetics: Applied Research. 2014; 12(2): 74-80. (in Russian)].
  27. Moreau P., Contu L., Alba F., Lai S., Simoes R., Orrù S. et al. HLA-G gene polymorphism in human placentas: possible association of G*0106 allele with preeclampsia and miscarriage. Biol. Reprod. 2008; 79(3): 459-67.https://dx.doi.org/10.1095/biolreprod.108.068874.
  28. Veit T.D., Vianna P., Scheibel I., Brenol C.V., Brenol J.C., Xavier R.M. et al. Association of the HLA-G 14-bp insertion/deletion polymorphism with juvenile idiopathic arthritis and rheumatoid arthritis. Tissue Antigens. 2008; 71(5): 440-6. https://dx.doi.org/10.1111/j.1399-0039.2008.01019.x.
  29. Zhuang B., Shang J., Yao Y. HLA-G: An important mediator of maternal-fetal immune-tolerance. Front. Immunol. 2021; 12: 744324.https://dx.doi.org/10.3389/fimmu.2021.744324.
  30. LeMaoult J., Daouya M., Wu J., Loustau M., Horuzsko A., Carosella E.D. Synthetic HLA-G proteins for therapeutic use in transplantation. FASEB J. 2013; 27(9): 3643-51. https://dx.doi.org/10.1096/fj.13-228247.
  31. Arnaiz-Villena A., Juarez I., Suarez-Trujillo F., López-Nares A., Vaquero C., Palacio-Gruber J., Martin-Villa J.M. HLA-G: Function, polymorphisms and pathology. Int. J. Immunogenet. 2021; 48(2): 172-92. https://dx.doi.org/10.1111/iji.12513.
  32. Aruna M., Sudheer P.S., Andal S., Tarakeswari S., Reddy A.G., Thangaraj K., Singh L., Reddy B.M. HLA-G polymorphism patterns show lack of detectable association with recurrent spontaneous abortion. Tissue Antigens. 2010; 76(3): 216-22. https://dx.doi.org/10.1111/j.1399-0039.2010.01505.x.
  33. Sipak-Szmigiel O., Cybulski C., Lubinski J., Ronin-Walknowska E. HLA-G polymorphism in a Polish population and reproductive failure. Tissue Antigens. 2008; 71(1): 67-71. https://dx.doi.org/10.1111/j.1399-0039.2007.00942.x.
  34. Gazit E., Slomov Y., Goldberg I., Brenner S., Loewenthal R. HLA-G is associated with pemphigus vulgaris in Jewish patients. Hum. Immunol. 2004; 65(1): 39-46. https://dx.doi.org/10.1016/j.humimm.2003.09.019.
  35. Monti M., Lupoli R., Sosa Fernandez L.M., Cirillo F., Di Minno M.N.D. Association of human leukocyte antigen-G 14 bp polymorphism with recurrent pregnancy loss in European countries: a meta-analysis of literature studies. Fertil. Steril. 2019; 112(3): 577-85.e3. https://dx.doi.org/10.1016/j.fertnstert.2019.05.003.
  36. Fan W., Li S., Huang Z., Chen Q. Relationship between HLA-G polymorphism and susceptibility to recurrent miscarriage: a meta-analysis of non-family-based studies. J. Assist. Reprod. Genet. 2014; 31(2): 173-84.https://dx.doi.org/10.1007/s10815-013-0155-2.
  37. Sipak O., Rył A., Grzywacz A., Laszczyńska M., Zimny M., Karakiewicz B. et al. The relationship between the HLA-G polymorphism and sHLA-G levels in parental pairs with high-risk pregnancy. Int. J. Environ. Res. Public Health. 2019; 16(9):1546. https://dx.doi.org/10.3390/ijerph16091546.

Received 15.11.2022

Accepted 09.02.2023

About the Authors

Margarita O. Shengelia, Junior Researcher, D.O. Ott, Research Institute of Obstetrics, Gynecology and Reproductology, +7(911)273-65-38, bakleicheva@gmail.com,
https://orcid.org/0000-0002-0103-8583, 199034, Russia, Saint-Petersburg, Mendeleyevskaya Liniya, 3.
Olesya N. Bespalova, Dr. Med Sci., Deputy Director for Research, D.O. Ott, Research Institute of Obstetrics, Gynecology and Reproductology,
+7(911)995-00-96, shiggerra@mail.ru, https://orcid.org/0000-0002-6542-5953, 199034, Russia, Saint-Petersburg, Mendeleyevskaya Liniya, 3.
Tatyana E. Ivashchenko , Dr. Dio. Sci., Professor, Leading Researcher at the Medical Genetic Center (Department of Genomic Medicine), D.O. Ott, Research Institute
of Obstetrics, Gynecology and Reproductology, +7(981)420-04-17, tivashchenko2011@mail.ru, https://orcid.org/0000-0002-8549-6505,
199034, Russia, Saint-Petersburg, Mendeleyevskaya Liniya, 3.
Nadezhda I. Frank, nurse at the Medical Genetic Center, D.O. Ott, Research Institute of Obstetrics, Gynecology and Reproductology,
+7(904)331-37-57, ncotta@mail.ru, 199034, Russia, Saint-Petersburg, Mendeleyevskaya Liniya, 3.
Iskender Yu. Sultanov, laboratory assistant-researcher at the Laboratory of genomics with a group of bioresource collections, D.O. Ott, Research Institute of Obstetrics, Gynecology and Reproductology, +7(921)893-14-23, 199034, Russia, Saint-Petersburg, Mendeleyevskaya Liniya, 3.
Yulia A. Nasykhova, Ph.D. (Bio), Head of the Genomics Laboratory with a group of bioresource collections, D.O. Ott, Research Institute of Obstetrics, Gynecology and Reproductology, +7(911)761-97-15, yulnasa@gmail.com, https://orcid.org/0000-0002-3543-4963, 199034, Russia, Saint-Petersburg, Mendeleyevskaya Liniya, 3.
Andrey S. Glotov, Dr. Bio. Sci., Head of the Medical Genetic Center, D.O. Ott, Research Institute of Obstetrics, Gynecology and Reproductology, +7(921)322-53-80, anglotov@mail.ru, https://orcid.org/0000-0002-7465-4504, 199034, Russia, Saint-Petersburg, Mendeleyevskaya Liniya, 3.
Corresponding author: Margarita O. Shengelia, bakleicheva@gmail.com

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