Indicators of the functions of the hepatobiliary system in patients with chronic opisthrochisis with genetic predisposition to the development of arterial hypertension

To assess the influence of genetic features associated with the development of arterial hypertension on the reactivity of the hepatobiliary system in opisthorchiasis invasion, a study of biochemical parameters was conducted in subgroups of patients with chronic opisthorchiasis with and without mutations in loci associated with a predisposition to this disease. It was found that the presence of a mutation in the rs1042713 locus of the ADRB2 gene increases deviations in ALP activity from the level of healthy individuals caused by opisthorchiasis invasion and slows down the normalization of ALT activity, but accelerates the decrease in cholesterol levels after treatment. Similar effects on ALP activity and ALT reaction after treatment are exerted by the AGT rs4762 polymorphism. The effect of another polymorphism of the same gene (AGT rs699) in CO seems to be rather positive: lower values of GGT activity and a decrease in ALT activity and cholesterol levels in response to therapy indicate less damage and faster normalization of hepatocyte functions. In the presence of the mutant allele of AGTR1 rs5186, liver dysfunctions in chronic opisthorchiasis are apparently aggravated (ALT activity and bilirubin levels are higher, alkaline phosphatase activity increases after treatment, although the bilirubin level decreases at this stage). The presence of a rare allele in the rs1799983 locus of the NOS3 gene in patients with opisthorchiasis prevents an increase in AM activity, but slows down the normalization of ALT and GGT activity after treatment. The effects of the studied polymorphisms on the process of changing biochemical parameters during therapy do not allow us to draw unambiguous conclusions, but may indicate a predominantly positive effect on the state of the hepatobiliary system in chronic opisthorchiasis of mutations in the AGT rs699 and NOS3 rs1799983 loci, and a predominantly negative effect in the ARDB2 rs1042713, AGT rs4762 and AGTR1 rs5186 loci.

1. Bakshtanovskaya I.V., Stepanova K.B., Ozerova A.N., Stepanova T.F., Zmatrakova E.A. Indicators of hepatobiliary system functions in patients with chronic opisthorchiasis with a genetic predisposition to lipid metabolism disorders. Med parasitol Mosk. 2023; 4:22-29. - in Russian. Doi: 10.33092/0025-8326mp2023.4.22-29

2. Bakshtanovskaya I.V., Stepanova K.B., Kal’gina G.A., Stepanova T.F. Relationships between biochemical and immunological parameters in patients with chronic opisthorchiasis. Med parasitol Mosk. . 2018; 2:13-19. - in Russian.

3. Kostyukevich O.I. Arterial hypertension and liver diseases: in search of a compromise. Russian Medical Journal: Independent publication for practicing physicians. 2011. v. 19, no. 5. pp. 338-342. - in Russian.

4. Morozova T.E., Rykova S.M., Shmarova D.G. Principles of choosing antihypertensive therapy in patients with metabolic syndrome and concomitant nonalcoholic fatty liver disease. Experimental and Clinical Gastroenterology. 2016, issue 130. No. 6. pp. 95-99. - in Russian.

5. Perticone M., Maio R., Caroleo B., et al. Serum γ-Glutamyltransferase concentration predicts endothelial dysfunction in naïve hypertensive patients. Biomedicines. 2020;8(7):207. doi:10.3390/biomedicines8070207.

6. Galasso G., De Rosa R., Ciccarelli M., et al. β2-Adrenergic receptor stimulation improves endothelial progenitor cell-mediated ischemic neoangiogenesis. Circ. Res. 2013; 112 (7): 1026-1034. doi:10.1161/CIRCRESAHA.111.300152

7. Almenara S., Lozano B., Gimenez P., et al. Functionality of beta-adrenergic receptors in patients with cirrhosis treated chronically with non-selective beta-blockers. Hepatol Int. 2020;14(5):858-868. doi:10.1007/s12072-020-10083-5.

8. Bulatova I.A., Shchekotova A.P., Krivtsov A.V., Shchekotov V.V., Nasibullina N.I., Suzdal'tseva K.N., Zhizhilev E.V. Metabolic disorder and polymorphism of the genes encoding for beta-2-adrenergic receptor and apolipoproteins B in chronic hepatitis C and nonalcoholic fatty liver diseases. Klin. Med. (Mosk). 2015;93(1):35-41. - in Russian.

9. Shahid M., Rehman K., Akash M.S.H., et al. Genetic Polymorphism in Angiotensinogen and Its Association with Cardiometabolic Diseases. Metabolites. 2022;12(12):1291. doi:10.3390/metabo12121291.

10. Akash M.S.H., Shahid M., Suhail S., Rehman K., Nadeem A., Mir T.M. Tetra-ARMS PCR analysis of angiotensinogen AGT T174M (rs4762) genetic polymorphism in diabetic patients: a comprehensive study. Front. Endocrinol. (Lausanne). 2023;14:1240291. doi:10.3389/fendo.2023.1240291.

11. Musso G., Saba F., Cassader M., et al. Angiotensin II type 1 receptor rs5186 gene variant predicts incident NAFLD and associated hypertension: role of dietary fat-induced proinflammatory cell activation. Am. J. Gastroenterol. 2019;114(4): 607-619. doi:10.14309/ajg.0000000000000154.

12. Eshraghian A., Taghavi A., Nikoupour H., Nikeghbalian S., Malek-Hosseini S.A. Angiotensin receptor blockers might be protective against hepatic steatosis after liver transplantation. BMC Gastroenterol. 2023; 23 (1): 152. doi:10.1186/s12876-023-02781-9.

13. Dong J., Ping Y., Wang Y., Zhang Y. The roles of endothelial nitric oxide synthase gene polymorphisms in diabetes mellitus and its associated vascular complications: a systematic review and meta-analysis. Endocrine. 2018;62(2):412-422. doi:10.1007/s12020-018-1683-4.

14. Pawlik A., Błaszczyk H., Rać M., Maciejewska-Skrendo A., Safranow K., Dziedziejko V. NOS3 gene rs1799983 and rs2070744 polymorphisms in patients with unstable angina. J. Vasc. Res. 2020;57(3):136- 142. doi:10.1159/000506160.

15. Tang C., Cao D., Wang L. The association between SNPs and hepatitis B virus related acute-on-chronic liver failure. Infect. Genet. Evol. 2020;86:104615. doi:10.1016/j.meegid.2020.104615.

16. Luo Z., Jia A., Lu Z., Muhammad I., Adenrele A., Song Y. Associations of the NOS3 rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and metaanalysis. Postgrad. Med. J. 2019;95(1125):361-371. doi:10.1136/postgradmedj-2019-136396.

17. Sapena V., Iavarone M., Boix L., et al. Polymorphism AGT2 (rs4762) is involved in the development of dermatologic events: proof of concept in hepatocellular carcinoma patients treated with sorafenib. World. J. Hepatol. 2022;14(7):1438-1458. doi:10.4254/wjh.v14.i7.1438.

18. Bogdanov A.O., Prokudina D.V., Baikov A.N., Saltykova I.V. Molecular mechanisms mediating the development of cholangiocarcinoma during chronic invasion by liver flukes // Siberian Journal of Oncology. 2015. No. 6, pp. 83-90. - in Russian.

19. Park M.J., Choi K.M. Association between variability of metabolic risk factors and cardiometabolic outcomes. Diabetes. Metab. J. 2022;46(1):49-62. doi:10.4093/dmj.2021.0316.

20. Ferrannini G., Rosenthal N., Hansen M.K., Ferrannini E. Liver function markers predict cardiovascular and renal outcomes in the CANVAS Program. Cardiovasc Diabetol. 2022;21(1):127. doi:10.1186/s12933-022-01558-w.