- Pecularities of the functional state of liver in children with inflammatory bowel diseases depending on variants of detoxification system gene polymorphism
Pecularities of the functional state of liver in children with inflammatory bowel diseases depending on variants of detoxification system gene polymorphism
PERINATOLOGIYA I PEDIATRIYA. 2017.2(70):134-139; doi 10.15574/PP.2017.70.134
Berezenko V. S., Tkalik E. N., Rossokha Z. I.
SI «Institute of Pedietrics, Obstetrics and Gynecology of NAMS of Ukraine», Kyiv
SI «Reference0centre for molecular diagnostic of the Ministry of Healthcare of Ukraine», Kyiv
Objective. To conduct research of the functional liver state features in children afflicted with inflammatory bowel diseases depending on detoxification system gene polymorphism (CYP2D6*4, GSTM1, GSTT1, MDR1).
Materials and methods. The study involved 44 children aged from 3 to 18, suffering from inflammatory bowel diseases. Functional liver state was estimated based on the main blood biochemical values, which characterise cytolytic, cholestatic and immunoinflammatory syndromes. The deletion polymorphism of GSTM1, GSTT1 genes was studied using the polymerase chain reaction, whereas the polymorphic variants of the CYP2D6*4(G1934A) and MDR1 (С3435Т) genes were detected by means of the polymerase chain reaction with the subsequent analysis of rstriction fragment length polymorphism.
Results. No reliable difference in frequency of polymorphic variants of studied genes was established in children with UC and CD. No correlation between functional liver state disorder and variants of first and second phase of detoxification genes polymorphism was found. Functional liver state disorder in form of cytolytic and immunoinflammatory syndromes was featured prominently in children with TT-genotype of the MDR1 gene.
Key words: children, inflammatory bowel diseases, functional liver state, detoxification genes.
1. Gusmanova GT, Kalimullina DH, Husainova RI. (2011). Klinicheskie assotsiatsii polimorfnyih variantov genov detoksikatsii ksenobiotikov pri tsirozah pecheni. Meditsinskiy vestn. Bashkorostana. 3: 71—76.
2. Berezenko VS, Tkalik EN, Rossokha ZI, Dyba MB. (2016). The study prevalence of polymorphisms of genes of detoxification system in children with inflammatory bowel disease. Perinatologiya i pediatriya. 3(67): 118—122. doi 10.15574/PP.2016.67.118
3. Musin AG, Hazieva AV, Nigmatullina AE et al. (2014). Polimorfizm genov sistemyi detoksikatsii ksenobiotikov, ego rol v biotransformatsii lekarstvennyih preparatov. Meditsinskiy vestn Bashkirostana. 9: 211—216.
4. Timucin M, Alagozlu H, Ozdemir S et al. (2013). Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus. Hepat Mon. 13(4): 7522. https://doi.org/10.5812/hepatmon.7522; PMid:23805158 PMCid:PMC3693542
5. Ruemmele FM, Veres G, Kolho KL et al. (2014). Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. J Crohns Colitis. 8(10): 1179—207. https://doi.org/10.1016/S1873-9946(14)50148-1; https://doi.org/10.1016/j.crohns.2014.04.005
6. Baldissera VD, de Mattos AA, Coral GP et al. (2012). Evaluation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma. Hepatol. 11(6): 899—906.
7. Kandemir O, Tamer L, Tasdelen B et al. (2008). Effects of GSTT1 GSTM1 and GSTP1 gene polymorphism on the course of hepatitis B virus infection. Hepatogastroenterology. 55: 1729-1733. PMid:19102379
8. Ladero JM, Martiez C, Garci-Marti E et al. (2006). Glutathione S transferase M1 and T1 genetic polymorphisms are not releated to the risk of hepatocellular carcinoma: a study in the Spanish population. Eur J Cancer. 42: 73—77. https://doi.org/10.1016/j.ejca.2005.08.033; PMid:16314088
9. Yu L, Wang CY, Xi B et al. (2011). GST polymorphisms are associated with hepatocellular carcinoma risk in Chinese population. World J Gastroenterol. 17: 3248—3256. PMid:21912475 PMCid:PMC3158402
10. Kimura Yasuhiko, Carlo Selmi, Patrick SC. (2005). Leung Genetic polymorphisms influencing xenobiotic metabolism and transport in patients with primary biliary cirrhosis. Hepatology. 1: 55-63.
11. Mohammadzadeh GS, Yaghmaei B, Allameh A et al. (2006). Polymorphisms of glutathione S transferase M1 T1 and P1 in patients with HBV related liver cirrhosis chronic hepatitis and normal carriers. Clin Biochem. 39: 46—49. https://doi.org/10.1016/j.clinbiochem.2005.10.004; PMid:16316639
12. Nebert DW, Russell DW. (2002). Clinical importance of the cytochromes P450. Lancet. 360(9340): 1155—62. https://doi.org/10.1016/S0140-6736(02)11203-7
13. Nieto N, Greenwel P, Friedman SL. (2000). Ethanol and Arachidonic Acid Increase a2(I) Collagen Expression in Rat Hepatic Stellate Cells Overexpressing Cytochrome P450 2E1. The Journal of Biological Chemistry: 20136—20145. https://doi.org/10.1074/jbc.M001422200; PMid:10770928
14. Parola M, Robino G. (2011). Oxidative stress-related molecules and liver fibrosis. J Hepatol. 35: 297—306. https://doi.org/10.1016/S0168-8278(01)00142-8
15. Burim RV, Canalle R, Martinelli Ade L et al. (2004). Polymorphisms in glutathione S-transferases GSTM1, GSTT1 and GSTP1 and cytochromes P4502E1 and CYP1A1 and susceptibility to cirrhosis or pancreatitis in alcoholics. Mutagenesis. 19: 291—298. https://doi.org/10.1093/mutage/geh034; PMid:15215328
16. Dignass A, Lindsay JO et al. (2012). Second European evidenceAbased Consensus on the diagnosis and management of ulcerative colitis: Defenitions and diagnosis (2012). Journal of Crohns and Colitis. 09. 002.
17. Tongmeng Yan, Linlin Lu, Cong Xie et al. (2015). Severely Impaired and Dysregulated Cytochrome P450 Expression and Activities in Hepatocellular Carcinoma: Implications for Personalized Treatment in Patients. Mol Cancer Ther. 14(12): 2874—2886. https://doi.org/10.1158/1535-7163.MCT-15-0274; PMid:26516155 PMCid:PMC4674380
18. Wang ZC, Liu LZ, Liu XY. (2015). Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma. Tumour Biol. 36(9): 7007—15. https://doi.org/10.1007/s13277-015-3407-1.