UDC

[612.17+616.12]:616-056.7

DOI

10.37482/2542-1298-Z007

Authors

Anna V. Tsepokina* ORCID: 0000-0002-4467-8732
Andrey V. Shabaldin*/** ORCID: 0000-0002-8785-7896
Svetlana A. Shmulevich*** ORCID: 0000-0002-7316-2962
Nadezhda S. Deeva*/** ORCID: 0000-0002-6162-4808
Anastasiya V. Ponasenko* ORCID: 0000-0002-3002-2863
Elena V. Shabaldina** ORCID: 0000-0002-0450-2767
*Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation)
**Kemerovo State Medical University (Kemerovo, Russian Federation)
***Kemerovo Regional Cardiological Dispensary (Kemerovo, Russian Federation)
Corresponding author: Anna Tsepokina, address: Sosnovyy bul’var 6, Kemerovo, 650002, Russian Federation; e-mail: cepoav1991@gmail.com

Abstract

Congenital heart defects (CHDs) are structural anomalies of the heart or great vessels occupying a leading place among fetal pathologies. It has been shown earlier that sporadic CHDs unrelated to chromosomal diseases are embryopathies associated with inflammation in the mother-embryo system. Transmitted and non-transmitted parental HLA-DRB1 alleles can determine inflammation. This research aimed to identify the associations of transmitted and non-transmitted parental HLA-DRB1 alleles with sporadic CHDs in children. We examined 48 families having children with CHDs (main group) and 132 families having two or more healthy children (control group). The frequency of 14 alleles of the HLA-DRB1 gene was determined. HLA-DRB1*10 was found to be significantly more common in mothers having children with sporadic CHDs than in the control group (p = 0.0132). Moreover, fathers of children with CHDs had no HLA-DRB1*13, while it was identified in 11 men from the control group (p = 0.016). The analysis of transmitted and non-transmitted alleles showed that HLA-DRB1*13 was less often inherited by children, compared to other alleles. The new results obtained in this research can be used both in fundamental and applied medicine to predict the risk for CHDs.
For citation: Tsepokina A.V., Shabaldin A.V., Shmulevich S.A., Deeva N.S., Ponasenko A.V., Shabaldina E.V. Features of the Inheritance of HLA-DRB1 Alleles in Families Having Children with Congenital Heart Defects. Journal of Medical and Biological Research, 2020, vol. 8, no. 2, pp. 166–173. DOI: 10.37482/2542-1298-Z007

Keywords

congenital heart disease, HLA-DRB1, transmitted alleles, non-transmitted alleles

References

1. Bokeriya L.A., Gudkova R.G. Serdechno-sosudistaya khirurgiya – 2014. Bolezni i vrozhdennye anomalii sistemy krovoobrashcheniyа [Cardiovascular Surgery – 2014. Diseases and Congenital Malformations of the Circulatory System]. Moscow, 2015. 226 p.
2. Williams K., Carson J., Lo C. Genetics of Congenital Heart Disease. Biomolecules, 2019, vol. 9, no. 12, Art. no. 879. DOI: 10.3390/biom9120879
3. Shabaldin A.V., Shmulevich S.A., Glebova L.A., Tsepokina A.V., Schastlivtsev E.L., Potapov V.P. Epidemiologicheskie i mediko-sotsial’nye aspekty vrozhdennykh porokov serdtsa u detey krupnogo promyshlennogo tsentra [Epidemiological, Medical and Social Aspects of Congenital Heart Defects in Children Living in Large Industrial Center]. Pediatriya. Zhurnal im. G.N. Speranskogo, 2016, vol. 95, no. 1, pp. 158–159.
4. Yu D., Feng Y., Yang L., Da M., Fan C., Wang S., Mo X. Maternal Socioeconomic Status and the Risk of Congenital Heart Defects in Offspring: A Meta-Analysis of 33 Studies. PLoS One, 2014, vol. 9, no. 10. Art. no. e111056. DOI: 10.1371/journal.pone.0111056
5. Erlebacher A. Immunology of the Maternal-Fetal Interface. Annu. Rev. Immunol., 2013, vol. 31, pp. 387–411. DOI: 10.1146/annurev-immunol-032712-100003
6. Inada K., Shima T., Nakashima A., Aoki K., Ito M., Saito S. Characterization of Regulatory T Cells in Decidua of Miscarriage Cases with Abnormal or Normal Fetal Chromosomal Content. J. Reprod. Immunol., 2013, vol. 97, no. 1, pp. 104–111. DOI: 10.1016/j.jri.2012.12.001 7. Mjösberg J., Berg G., Jenmalm M.C., Ernerudh J. FOXP3+ Regulatory T Cells and T Helper 1, T Helper 2, and T Helper 17 Cells in Human Early Pregnancy Decidua. Biol. Reprod., 2010, vol. 82, no. 4, pp. 698–705. DOI: 10.1095/ biolreprod.109.081208
8. Gazieva I.A., Chistyakova G.N., Remizova I.I. Rol’ narusheniy produktsii tsitokinov v geneze platsentarnoy nedostatochnosti i rannikh reproduktivnykh poter’ [Role of Cytokine Production Disorders in Genesis of Placental Insufficiency and Early Reproductive Losses]. Meditsinskaya immunologiya, 2014, vol. 16, no. 6, pp. 539–550.
9. Ceyran A.B., Şenol S., Güzelmeriç F., Tunçer E., Tongut A., Özbek B., Şavluk Ö., Aydın A., Ceyran H. Effects of Hypoxia and Its Relationship with Apoptosis, Stem Cells, and Angiogenesis on the Thymus of Children with Congenital Heart Defects: A Morphological and Immunohistochemical Study. Int. J. Clin. Exp. Pathol., 2015, vol. 8, no. 7, pp. 8038–8047.
10. Jurewicz M.M., Stern L.J. Class II MHC Antigen Processing in Immune Tolerance and Inflammation. Immunogenetics, 2019, vol. 71, no. 3, pp. 171–187.
11. Khaitov R.M., Alekseev L.P., Kofiadi I.A. Rol’ immunogenetiki v reshenii fundamental’nykh i prikladnykh zadach personalizirovannoy meditsiny [Role of Immunogenetics in Addressing Fundamental and Applied Tasks of Personalized Medicine]. Meditsina ekstremal’nykh situatsiy, 2016, no. 3, pp. 9–24.
12. Hansen C.A., Barnett A.G., Jalaludin B.B., Morgan G.G. Ambient Air Pollution and Birth Defects in Brisbane, Australia. PLoS One, 2009, vol. 4, no. 4. Art. no. e5408. DOI: 10.1371/journal.pone.0005408
13. Tsepokina A.V., Shabaldin A.V., Litvinova N.A., Shmulevich S.A. Rol’ polimorfnykh variantov HLA-DRB1* v razvitii vrozhdennykh porokov serdtsa [The Role of Polymorphic Variants of the HLA-DRB1* Gene in the Development of Congenital Heart Diseases]. Sibirskiy meditsinskiy zhurnal, 2016, vol. 31, no. 2, pp. 63–66.
14. Boldyreva M.N., Alekseev L.P. HLA i estestvennyy otbor. Gipoteza “preimushchestva funktsional’noy geterozigotnosti” [HLA and Natural Selection. Hypothesis of “Functional Heterozygosity Preference”]. Immunologiya, 2006, vol. 27, no. 3, pp. 172–176.
15. Guthrie K.A., Tishkevich N.R., Nelson J.L. Non-Inherited Maternal Human Leukocyte Antigen Alleles in Susceptibility to Familial Rheumatoid Arthritis. Ann. Rheum. Dis., 2008, vol. 68, no. 1, pp. 107–109. DOI: 10.1136/ard.2008.092312
16. Gordeeva L.A., Shabaldin A.V., Glushkov A.N. Vliyanie neunasledovannykh roditel’skikh HLA na immunnyy otvet u potomstva [Effects of Non-Inherited Parental HLA-Antigens Upon Immune Response in Progeny]. Meditsinskaya immunologiya, 2006, vol. 8, no. 5-6, pp. 587–596.
17. Khaitov R.M., Alekseev L.P., Boldyreva M.N. Novye predstavleniya o fiziologicheskoy roli HLA-genov v reproduktivnom protsesse [New Ideas of the Physiological Role of HLA Genes in the Reproductive Process]. Rossiyskiy fiziologicheskiy zhurnal im. I.M. Sechenova, 2006, vol. 92, no. 4, pp. 393–401.