Association of HIF-1A (rs11549465) gene polymorphism with congenital malformations and intrauterine growth retardation of the fetus

Introduction. Congenital malformations have long received the status of a marker of environmental distress. Six per cent of the newborns in the world are diagnosed with congenital malformations of various etiologies, 30 million develop intrauterine growth retardation, often associated with hypoxia, while the number of these pathologies is significantly higher in environmentally unfavourable regions.

The degree of resistance to hypoxia is determined by the transcription factor induced by hypoxic conditions — HIF. There is revealed polymorphism of the HIF gene, which determines the differences in the activity of the transcription factor encoded by this gene, and therefore, the differences in the level of resistance to hypoxia. Recently, HIF has also been detected in response to the activation of free radical processes.

Materials and methods. The study examined fifty five women living in the South of Kuzbass, most of them in the city of Novokuznetsk. 18 women were included in the control group because they carried a healthy child, the study group consisted of 11 women who gave birth to children with intrauterine growth retardation, and 26 women who gave birth to children with congenital malformations.

Genomic DNA was isolated from peripheral blood leukocytes using the phenol-chloroform extraction method. Gene typing was carried out by the Real Time method.

Results. Among the studied groups, in women who gave birth to children with congenital malformations, there were no reliable differences in the occurrence of polymorphisms of mutant and wild types. In the group of women who gave birth to children with intrauterine growth retardation, a reliable association of C/T polymorphism in the mother with intrauterine fetal growth retardation was shown (χ² = 4.54; OR = 9.71), while the ancestral form of C/C was associated with resistance to this pathology.

Limitations. Since the identification of the association of the HIF-1А (rs11549465) gene polymorphism with intrauterine growth retardation was of a pilot nature, it is advisable to increase the sample.

Conclusion. The results obtained may indicate the leading role of the HIF-α subunit in the body’s adaptation to hypoxia and the secondary importance of this protein in the regulation of pro- and antioxidant balance.

Compliance with ethical standards. The examination of the patients complied with the ethical standards of the Bioethical Committee of the Research Institute for Complex Problems of Hygiene and Occupational Diseases, developed in accordance with the Helsinki Declaration of the World Association “Ethical Principles of Conducting Scientific Medical Research with Human Participation” as amended in 2013 and “Rules of Clinical Practice in the Russian Federation”, approved by the Order of the Ministry of Health of the Russian Federation No. 266 of June 19, 2003. All participants signed an informed consent to participate in the study.

Contribution:
Gulyaeva O.N. — concept and design of the study, collection and processing of material, statistical processing, editing;
Kazitskaya A.S. — collection and processing of material;
Zhukova A.G. — editing;
Zagorodnikova O.A. — collection and processing of material;
Alekseeva M.V. — collection and processing of material;
Renge L.V. — concept and design of the study.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study had no sponsorship.

Received: March 17, 2022 / Accepted: June 08, 2022 / Published: July 31, 2022