Assessment of the contribution of UGT1A gene polymorphisms to the development of cholelithiasis
https://doi.org/10.31146/1682-8658-ecg-218-10-133-138
Abstract
Iron overload in non-alcoholic fatty liver disease (NAFLD) is a fairly common phenomenon that receives very little attention in clinical practice. However, iron overload, leading to hemosiderosis (deposition of “indigestible” nanodispersed iron oxides in various tissues) significantly aggravates NAFLD, stimulating increased chronic inflammation, insulin resistance and hemosiderosis of other organs. As a result, ferroptosis of hepatocytes occurs (apoptosis caused by iron overload and hemosiderosis), which accelerates the transformation of non-alcoholic steatosis into non-alcoholic steatohepatitis (NASH) and, subsequently, into liver cirrhosis. Iron overload is aggravated by micronutrient deficiencies and pathogenic intestinal microbiota. The paper presents the results of a systematic analysis of this issue, describes the prospects for therapy using micronutrients and human placenta hydrolysates (HPP), which contribute not only to the regeneration of liver tissue, but also to the normalization of iron homeostasis.
About the Authors
E. V. Shreiner
Novosibirsk State University; Institute of chemical, Institute of Chemical Biology and Fundamental Medicine of the SB RAS
Russian Federation
Russian Federation
A. I. Khavkin
Research Clinical Institute of Childhood, Ministry of Health of the Moscow Region; Belgorod State Research University
Russian Federation
Russian Federation
M. S. Novikova
Novosibirsk State University
Russian Federation
Russian Federation
N. V. Kokh
Novosibirsk State University; Institute of chemical, Institute of Chemical Biology and Fundamental Medicine of the SB RAS
Russian Federation
Russian Federation
M. Yu. Denisov
Novosibirsk State University
Russian Federation
Russian Federation
G. I. Lifshits
Novosibirsk State University; Institute of chemical, Institute of Chemical Biology and Fundamental Medicine of the SB RAS
Russian Federation
Russian Federation
References
1. Vítek L., Tiribelli C. Gilbert’s syndrome revisited. J Hepatol. 2023 Oct;79(4):1049-1055. doi: 10.1016/j.jhep.2023.06.004.
2. Frybova B., Drabek J., Lochmannova J., Douda L., Hlava S., Zemkova D. et al. Cholelithiasis and choledocholithiasis in children: risk factors for development. PLoS One. 2018. 13(5): e0196475. doi:10.1371/journal.pone.0196475.
3. Kim J., Cheong H., Park B. et al.Comprehensive variant screening of the UGT gene family. Yonsei Med J. 2014. 55(1): 232-239. doi: 10.3349/ymj.2014.55.1.232.
4. Sidorenko D. V., Nazarov V. D., Volnikova E. G., Kondrasheva E. A., Peshkova N. G., Kovaleva I. S. et al. Dependence of blood biochemical parameters on various genotypes of the UGT1A1 gene associated with Gilbert’s syndrome. Klinicheskaja laboratornaja diagnostika (Russian Clinical Laboratory Diagnostics). 2022. 67(2): 69-75. (in Russ.) doi: 10.51620/0869-2084-2022-67-2-69-75. @@ Сидоренко Д. В., Назаров В. Д., Волникова Е. Г., Кондрашева Е. А., Пешкова Н. Г., Ковалева И. С. и др. Зависимость биохимических показателей крови от различных генотипов гена UGT1A1, ассоциированного с синдромом Жильбера. Клиническая лабораторная диагностика. 2022. Т. 67. № 2. С. 69-75. doi:10.51620/0869-2084-2022-67-2-69-75.
5. Barbarino J. M., Haidar C. E., Klein T. E., Altman R. B. PharmGKB summary: very important pharmacogene information for UGT1A1. Pharmacogenet Genomics. 2014 Mar;24(3):177-83. doi: 10.1097/FPC.0000000000000024.
6. Steventon G. Uridine diphosphate glucuronosyltransferase 1A1. Xenobiotica. 2020. 50(1): 64-76. doi:10.1080/00498254.2019.1617910.
7. Deming S. L., Zheng W., Xu W. H., Cai Q., Ruan Z., Xiang Y. B., Shu X. O. UGT1A1 genetic polymorphisms, endogenous estrogen exposure, soy food intake, and endometrial cancer risk. Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):563-70. doi: 10.1158/1055-9965.EPI-07-0752.
8. Agrawal V., Tiwari A., Sharma D., Agrawal R. Etiology-Based Decision-Making Protocol for Pediatric Cholelithiasis. Indian Pediatr. 2021. 58(8): 729-732.
9. Kurilovich S. A., Nemtsova E. G., Kruchinina M. V., Maximov V. N. Features of gilbert’s syndrome in patients with different genotypes UGT1A1. Experimental and Clinical Gastroenterology. 2016;(9):32-37. (In Russ.)
10. Sandra L. Deming, Wei Zheng, Wang-Hong Xu, Qiuyin Cai, Zhixian Ruan, Yong-Bing Xiang, Xiao-Ou Shu. UGT1A1 Genetic Polymorphisms, Endogenous Estrogen Exposure, Soy Food Intake, and Endometrial Cancer Risk. Cancer Epidemiol Biomarkers Prev 1 March 2008; 17 (3): 563-570. (in Russ.) doi: 10.1158/1055-9965.EPI-07-0752.@@ Новикова М. С., Шрайнер Е. В., Лифщиц Г. И., Кох Н. В., Хавкин А. И. Взаимосвязь желчнокаменной болезни и метаболического синдрома: роль генетических факторов. Экспериментальная и клиническая гастроэнтерология. 2022;(7):204-210. doi: 10.31146/1682-8658-ecg-203-7-204-210
11. Du Z, Xu H, Zhao P, Wang J, Xu Q, Liu M. Influence of UGT2B7 and UGT1A6 polymorphisms on plasma concentration to dose ratio of valproic acid in Chinese epileptic children. Xenobiotica. 2021 Jul;51(7):859-864. doi: 10.1080/00498254.2021.1931554.
12. Li M., Seiser E. L., Baldwin R. M., Ramirez J., Ratain M. J., Innocenti F., Kroetz D. L. ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia. Pharmacogenomics J. 2018 Jan;18(1):35-42. doi: 10.1038/tpj.2016.75.
13. Ferraldeschi R., Minchell L. J., Roberts S. A. et al. UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. Pharmacogenomics. 2009 May;10(5):733-9. doi: 10.2217/pgs.09.20.
14. Bhatt D. K., Mehrotra A., Gaedigk A. et al. Age- and Genotype-Dependent Variability in the Protein Abundance and Activity of Six Major Uridine Diphosphate-Glucuronosyltransferases in Human Liver. Clin Pharmacol Ther. 2019 Jan;105(1):131-141. doi: 10.1002/cpt.1109.
15. Ufimtseva I. V., Pirogova I.Yu., Sinitsyn S. P., Yakovleva S. V. Features of the course of gallstone disease in comorbid patients with non-alcoholic fatty liver disease. Experimental and Clinical Gastroenterology. 2022;(7):103-109. (in Russ.) doi: 10.31146/1682-8658-ecg-203-7-103-109.@@ Уфимцева И. В., Пирогова И. Ю., Синицын С. П., Яковлева С. В. Особенности течения ЖКБ у пациентов с неалкогольной жировой болезнью печени. Экспериментальная и клиническая гастроэнтерология. 2022;(7):103-109. doi: 10.31146/1682-8658-ecg-203-7-103-109.
16. Xiang G. Q., Sun F. R., Wang B. Y. [Gilbert’s syndrome: hyperbilirubinemia enemy or friend]. Zhonghua Gan Zang Bing Za Zhi. 2021 Oct 20;29(10):1024-1027. Chinese. doi: 10.3760/cma.j.cn501113-20200212-00041.
17. Vitek L., Jirsa M., Brodanova M. et al. Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis. 2002 Feb;160(2):449-56. doi: 10.1016/s0021-9150(01)00601-3.
18. Ivanov A., Semenova E. Gilbert’s Syndrome, Bilirubin Level and UGT1A1*28 Genotype in Men of North-West Region of Russia. J Clin Exp Hepatol. 2021 Nov-Dec;11(6):691-699. doi: 10.1016/j.jceh.2021.01.006.
19. Passon R.G, Howard T.A, Zimmerman S.A, Schultz W.H, Ware R. E. Influence of bilirubin uridine diphosphate-glucuronosyltransferase 1A promoter polymorphisms on serum bilirubin levels and cholelithiasis in children with sickle cell anemia. J Pediatr Hematol Oncol. 2001 Oct;23(7):448-51. doi: 10.1097/00043426-200110000-00011.
Review
For citations:
Shreiner E.V., Khavkin A.I., Novikova M.S., Kokh N.V., Denisov M.Yu., Lifshits G.I. Assessment of the contribution of UGT1A gene polymorphisms to the development of cholelithiasis. Experimental and Clinical Gastroenterology. 2023;(10):133-138. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-218-10-133-138
Views:
219
Email this article 