Pharmacogenetic approaches to hypertension treatment in pregnant women


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Abstract

Hypertension in pregnancy is an urgent problem of modern medicine due to its high prevalence (it occurs in 5-30% of pregnant women in the Russian Federation) and to the risk of maternal and fetal complications. Considering the complex and incompletely studied pathogenesis of hypertension during pregnancy, the selection of antihypertensive therapy (AHT) remains open and is now being actively studied. In recent years, prescription of AHT for pregnant women has come under consideration in the context of personalized medicine. The genetic characteristics of a patient, which affect a pharmacological response, are point mutations and the so-called single nucleotide polymorphisms. The existence of single nucleotide polymorphisms in one gene or another can define the genetically determined contribution to an individual’s pharmacological response. Endothelial dysfunction that is manifested inter alia by decreased nitric oxide (NO) synthesis is an important pathogenetic element in the development of hypertension in pregnant women. There is a relationship between endothelial NO synthase (eNOS) (NOS3) gene polymorphism and AHT responses in preeclampsia (PE). The ‘C- Glu-a’ and ‘T-Asp-a’ haplotypes were found to be associated with the presence and absence of the response, respectively. There was no association of vascular endothelial growth factor gene polymorphismbi (C-2578A rs699947) and (G-634C rs2010963) with AHT responses in PE. Taking into account the role of systemic inflammation in the development of hypertension in pregnant women, it seems important to study the level of proinflammatory cytokines, visfatin in particular, in these patients. The association between AHT responses and visfatin/NAMPTgene polymorphism is now being actively studied. The C, A haplotype was associated with AHT responses in patients with PE. Further investigation of genetic polymorphism and gene-drug interactions may contribute to the elaboration of new therapeutic approaches to prescribing AHT in pregnancy.

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About the authors

Evgenia V. Shikh

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: chih@mail.ru
MD, professor, head. Department of Clinical Pharmacology and Propaedeutics of Internal Medicine

Olga V. Zhukova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: dr_zhukova@mail.ru
candidate of medical sciences, assistant of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases I.M.Sechenova.

Olga D. Ostroumova

I.M. Sechenov First Moscow State Medical University (Sechenov University); A.I. Evdokimov Moscow State University of Medicine and Dentistry

Email: ostroumova.olga@mail.ru
MD, professor, professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases THEM. Sechenov, Professor, Department of Faculty Therapy and Occupational Diseases

Svetlana S. Sharonova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: lana.sh917@gmail.com
student

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