Association of gene polymorphisms of the reninangiotensin system and endothelial dysfunction with development and severity of portal hypertension in patients with chronic hepatitis C

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Background: At present, much attention is paid to genetic factors explaining the clinical course of chronic hepatitis C. Aim: To evaluate an association of the gene polymorphisms involved in the formation of endothelial dysfunction (NOS3 894G/T, CYBA 242C/T, MTHFR 677C/T) and encoding components of the renin-angiotensin system (ATR1 1166A/C, AGT (-6)G/T and 235M/T) with development and severity of portal hypertension syndrome in patients with chronic hepatitis C. Materials and methods: 162 patients with chronic hepatitis C and HCV-related cirrhosis (114 women and 48 men) were divided into the following groups: no portal hypertension (n = 98), "compensated" (n = 19) and "decompensated" (n = 45) portal hypertension. The gene polymorphisms were assessed by molecular genetic methods. Results: TT genotype of CYBA was more common in patients with portal hypertension than in those without (odds ratio (OR) for TT = 3.59, p = 0.031). This difference becomes larger when comparing the decompensated portal hypertension group with the no portal hypertension group (OR TT = 5.46, p = 0.009). Other gene polymorphisms were not associated with development or decompensation of portal hypertension. Multivariate analysis of the impact of genetic, clinical and demographic factors showed that portal hypertension was associated primarily with patients age at the time of the study (Wald's х2 = 14.99) and with their body mass index (Wald's х2 = 4.35). After exclusion of these population-wide risk factors from the model, the development of portal hypertension correlated with the carriage of 235TT genotype of CYBA (Wald's х2 = 6.07, OR = 4.29) and (-6)AA genotype AGT (Wald's х2 = 4.73, OR = 4.13), as well as with the lack of protective 235TT genotype AGT (Wald's х2 = 4.06, OR = 0.33). The combined effects of the studied gene polymorphisms on decompensation of the portal hypertension in patients with chronic HCV infection were similar. Conclusion: The development and increase in severity of portal hypertension syndrome in patients with chronic hepatitis C is directly correlated with the carriage of AA genotype of AGT (-6)G/A and TT genotype CYBA 242C/T and the absence of TT genotype AGT 235M/T.

About the authors

O. V. Taratina

Moscow Regional Research and Clinical Institute, Moscow

Author for correspondence.
Email: taratina.o@gmail.com

Taratina Olesya V. – MD, PhD, Research Fellow, Department of Gastroenterology and Hepatology.

61/2-9 Shchepkina ul., Moscow, 129110, Russian Federation. Tel.: +7 (926) 245 66 59. E-mail: taratina.o@gmail.com Россия

L. M. Samokhodskaya

Lomonosov Moscow State University, Moscow

Email: fake@neicon.ru
Samokhodskaya Larisa M. – MD, PhD, Associate Professor, Leading Research Fellow, Laboratory of Gene and Cell Technologies, Faculty of Basic Medicine Россия

T. N. Krasnova

Lomonosov Moscow State University, Moscow

Email: fake@neicon.ru
Krasnova Tatiana N. – MD, PhD, Associate Professor, Chair of Internal Medicine, Faculty of Basic Medicine Россия

N. A. Mukhin

Lomonosov Moscow State University, Moscow

Email: fake@neicon.ru
Mukhin Nikolay A. – MD, PhD, Professor, Member of Russian Academy of Sciences, Head of the Chair of Internal Medicine, Faculty of Basic Medicine Россия

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