Haiboniuk I., Kravchenko S., Makukh H., Dats-Opoka M., Pampukha V., Tretiak B., Kiselyk I.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Goal. To determine the prevalence of the low-functional allele A (TA)7 TAA of the UGT1A1 gene (rs8175347) among practically healthy residents of Ukraine and in the group of individuals with idiopathic hepatobiliary disorders and Gilbert’s syndrome. Methods. DNA extraction was performed by the method of salting out. Amplification of specific sequences was performed by PCR. The analysis of the amplified fragments was performed by 10% PAGE gel electrophoresis, fragment analysis of fluorescently labeled PCR products and HRM analysis (melting curve analysis). Results. The comparative analysis of the allelic polymorphism of the UGTA1 gene rs8175347 revealed no significant difference in the distribution of allele frequencies and genotypes between samples from the Western and Central regions of Ukraine. No significant differences were found in the distribution of alleles and genotypes between males and females, but clinically Gilbert’s syndrome was much more commonly found in young males. The frequency of associated with Gilbert’s syndrome the homozygous genotype A(TA)7 TAA of UGT1A1 gene is present among 10,7% of the total population of Ukraine. The frequency of the low-functional allele A (TA)7 TAA of the UGT1A1 gene in Ukraine is 33.8%.84,1% of patients with clinical manifestations of Gilbert’s syndrome are homozygous for UGT1A1 allele A(TA) 7 TAA, which allows genetically verifying the diagnosis. These studies indicate the high informativeness of genetic testing of the allele A (TA) 7TAA of the UGT1A1 gene among individuals with hyperbilirubinemia to rule out Gilbert syndrome. Genetically verified diagnosis allows you to assign the correct treatment, to take into account this feature when prescribing therapy with certain drugs, to increase alertness to the development of other comorbidities. Genetically verified diagnosis allows you to assign the correct treatment, to take into account this feature when prescribing therapy with certain drugs, to increase alertness to the development of other comorbidities. Conclusions. The incidence of the homozygous genotype A(TA)7 TAA of UGT1A1 gene associated with Gilbert syndrome in Ukraine is 10,7% Genetic testing of UGT1A1 gene A(TA)7 TAA allele among individuals with hyperbilirubinemia verified the diagnosis of Gilbert’s syndrome in 84,1% of patients.

hyperbilirubinemia, UGT1A1 gene, Gilbert syndrome, genetic diagnostic.

1. Sorokman TV, Popeliuk О-МV, Makarova ОV. Syndrom Zhylbera: terminologia, epidemiologia, genetyka, petogenez (chastyna 1). Zdorovia dytyny. 2016;8(76):82-6. DOI: 10.22141/2224-0551.8.76.2016.90830 [in Ukrainian].
2. Zhu XY, Liu LX. Ultrastructure of hepatocytes in Gilbert’s syndrome patients and chronic hepatitis B patients. Zhonghua Gan Zang Bing Za Zhi. 2013 Dec;21(12):929-33. DOI: 10.3760/cma.j.issn.1007-3418.2013.12.011
3. Shcherbinina MB, Pacienty z syndromom Zhylbera: nova taktyka vedennia. Zdorovia Ukrainy. Gastroenterologia. Gepatologia. Koloproctologia. 2014;4(34):49-50. [in Ukrainian].
4. Shulyat’ev YS. Syndrom Zhyl’bera: klynyka, dyahnostyka, funktsyonal’noe sostoyanye pecheny (klynyko-henetycheskoe yssledovanye) [dissertatsiya]. Moskva; 2005. 20 s. [in Russiаn].
5. Sorokman TV, Popeliuk О-МV, Makarova ОV. Syndrom Zhylbera: klinika, diagnostyka, dyferencialna diagnostyka ta likuvanna (chastyna 2). Zdorovia dytyny. 2017;12(1). DOI: http://dx.doi.org/10.22141/2224-0551.12.1.2017.95025 [in Ukrainian].
6. Varlamova OS. Viral hepatitis A and Gilbert’s syndrome. In: Conference on Hepatitis: modern views on the issue. 2016. s. 12-3.
7. Demirbas T, Piskin T, Dayangac M, Yaprak O, Akyildiz M, Tokat Y, Yuzer Y. Right-lobe liver trans-plant from donors with Gilbert syndrome. Exp Clin Transplant. 2012;10(1):39-42.
8. Kathemann S, Lainka E, Baba HA, Hoyer PF, Gerner P. Gilbert’s syndrome – a frequent cause of unconjugated hyperbilirubinemia in children after orthotopic liver transplantation. Pediatr Transplant. 2012;16(2):201-4. DOI: 10.1111/j.1399-3046.2012.01662.x
9. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. Circulation. 2012 Jul 31;126(5):598-603. DOI: 10.1161/circulationaha.112.105775
10. Shiu TY, Huang HH, Lin HH, Shih YL, Chu HC, Chang WK, Hsieh TY. Restriction fragment length polymorphism effectively identifies exon 1 mutation of UGT1A1 gene in patients with Gilbert’s Syndrome. Liver. Int. 2015 Aug;35(8):2050-6. DOI: 10.1111/liv.12785
11. Makukh HV, Zastavna DV, Tyrkus MYa. Pat. 32044 UA, MPK G01N33/49 (2006.01) Sposib vydilannia DNK z lejkocytiv peryferijnoi krovi, zaiavnyk DU «Instytut spadkovoi patologii NAMNU». № u200801896; zaiavl. 14.02.2008; opubl. 25.04.2008, Biul. № 8. [in Ukrainian].
12. Kamal S, Abdelhakam S, Ghoraba D, Massoud Y, Aziz KA, Hassan H, et al. The frequency, clinical course, and health related quality of life in adults with Gilbert’s syndrome: a longitudinal study. BMC Gastroenterol. 2019 Feb 04;19(1):22.
13. Haybonyuk I, Makukh H. Analiz nyzʹkofunktsionalʹnoyi aleli 7(TA) hena UGT1A1 sered vybirky praktychno zdorovykh osib zakhidnoho rehionu Ukrayiny. Visnyk Kharkivsʹkoho natsionalʹnoho universytetu im. N.V. Karazina. 2019;33:29-34. [in Ukrainian].

«Bulletin of problems biology and medicine» Issue 2 (156), 2020 year, 91-96 pages, index UDK 575.224.2:616.36

10.29254/2077-4214-2020-2-156-91-96