Relationship between the expression level of microRNA and the features of clinical course of the gallbladder and Оddi's sphincter functional disorders in children
Keywords:biliary dyskinesia, Oddi's sphincter dysfunction, genetic epigenesis, microRNA, children
The aim of the work is to establish the relationship between the expression levels of microRNA-378f, microRNA-4311, microRNA-4714-3p and anamnestic, clinical and paraclinical parameters of functional disorders of the gallbladder and Oddi's sphincter (FD GB and OS) in children.
Materials and methods. We examined 50 children with FD GB and OS aged from 4 to 14 years old. The control group included 20 healthy children of the same age. All the children, in addition to general clinical examination, underwent a molecular genetic study with the determination of the expression level of microRNA-378f, microRNA-4311, microRNA-4714-3p in blood serum by the method of real-time reverse transcription polymerase chain reaction according to TaqMan Gene Expression Assays protocol. In total, 140 clinical, laboratory and instrumental diagnostic indicators of 50 patients with verified FD GB and OS were analyzed using correlation analysis.
Results. Associations between the expression level of microRNA-378f and familial heredity of the biliary tract diseases with FD GB and OS in mothers (r = +0.27; P < 0.05) and sisters (r = +0.39; P < 0.05) of patients were identified. A positive correlation was registered between the expression levels of microRNA-378f and micro-RNA-4311 and FD GB and OS in maternal relatives (r = +0.35 and r = +0.32, respectively; P < 0.05). Associations between the expression levels of microRNA-4311 and microRNA-4714-3p and burdened allergic history in children with FD GB and OS (r = +0.41; r = +0.37, respectively; P < 0.05) were established. Analysis of the correlation diagram showed that the expression level of microRNA-4714-3p was positively correlated with a decrease in the gallbladder contractility (r = +0.36; P < 0.05).
Conclusions. Significant correlations between the expression levels of microRNA-378f and microRNA-4311 and familial aggregation of the biliary tract pathology in the pedigrees of children with FD GB and OS were established. It was determined that the burdened allergic history was associated with the expression levels of microRNA-4311 and micro-RNA4714-3p in the examined children. Associations between the expression levels of microRNA-4311 and microRNA-4714-3p and clinical manifestations of abdominal pain syndrome, dyspeptic and asteno-vegetative syndromes of FD GB and OS in children were found. It was revealed that a decrease in the expression level of microRNA-4714-3p was associated with a decrease in the gallbladder contractility in children with FD GB and OS.
Shadrin, O. G., Marushko, T. L., Radushinskaya, T. Yu., Marushko, R. V., Fisun, V. N., Kovalchuk, A. A., & Bondarenko, N. Y. (2016). Kharchova neperenosymіst u patoрenezі funktsіonalnykh zakhvoriuvan shlunkovo-kyshkovoho traktu v dіtei rannoho vіku: pіdkhody do dіahnostyky ta lіkuvannia [Food intolerance in the pathogenesis of functional gastrointestinal disorders in infants: approaches to diagnosis and treatment]. Рerinatolohiia i pediatriia, 1(65), 104–111. doi: 10.15574/PP.2016.65.104 [in Ukrainian].
Volosovets, O. P., Zubarenko, O. V., & Kryvopustov, S. P. (2017) Pedіatrіia (hastroenterolohіia ta patolohіia rannoho vіku) [Pediatrics (Gastroenterology and Pathology of the Early Age)]. Odesa. [in Ukrainian].
Maidannyk, V. G. (2016). Rymski kryterii IV (2016): shcho novoho? [Rome IV (2016) criteria: What is new?]. Mizhnarodnyi zhurnal pediatrii, akusherstva ta hinekolohii, 1(10), 8–18. [in Ukrainian].
(2013) Unifikovanyi klinichnyi protokol medychnoi dopomohy ditiam iz zakhvoriuvanniamy orhaniv travlennia : nakaz MOZ Ukrainy vid 29.01.2013. №59 [Unified clinical protocol of medical aid for children with diseases of the digestive system: Order of the Ministry of Health of Ukraine from January 29, 2013. №59]. Sovremennaya pediatriya, 4, 20–31. [in Ukrainian].
Marushko, U. V., Nagorna, K. I., & Bryuzgina, T. S. (2016). Klinichni proiavy i zhyrnokyslotnyi balans u ditei iz biliarnoiu dysfunktsiieiu i defitsytom zaliza [Clinical manifestation and fatty acid balance in children with biliary dysfunction and iron deficiency]. Perinatolohiia i pediatriia, 2(66), 116–121. doi: 10.15574/PP.2016.66.116 [in Ukrainian].
Tyazhka, O. V., Smishchuk, V. V., & Bryuzgina, T. S. (2015) Znachennia biokhimichnoho doslidzhennia zhovchi yak indykatora porushen metabolizmu zhyrnykh kyslot, fosfolipidiv ta kholesterynu v ditei z kholelitiazom [Importance of bile biochemical studies as an indicator of fatty acids, phospholipids and cholesterol metabolic disorders in children with cholelithiasis]. Perinatolohiia i pediatriia, 1(61), 63–67. doi: 10.15574/PP.2015.61.63 [in Ukrainian].
Vakhrushev, Ya. M., Khokhlacheva, N. А., Mikheevа, P. S., & Suchkova, Е. V. (2018) Mekhanizmy narushenij motorno-e'vakuatornoj funkcii zhelchnogo puzyrya i ikh znachenie v razvitii kholelitiaza [The mechanisms of the disorders of motor-evacuation function of gall bladder and their importance in the development of cholelithiasis]. Arhiv' vnutrennej mediciny, 1, 53–58. [in Russian].
Letelier, P., Riquelme, I., Hernández, A. H., Guzmán, N., Farías, J. G., & Roa, J. C. (2016) Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers. Int J Mol Sci., 17(5), 791. doi: 10.3390/ijms17050791
Panella, M., Carotenuto, P., & Braconi, C. (2018) MicroRNAs link inflammation and primary biliary cholangitis. Non-coding RNA Investig, 2, 29. doi: 10.21037/ncri.2018.05.02
Puik, J. R., Meijer, L. L., Le Large, T. Y., Heger, M., Dijk, F., Funel, N., et al. (2018) Circulating biliary tract microRNA signature discriminates cholangiocarcinoma from pancreatic cancer [abstract]. Proceedings of the American Association for Cancer Research Annual Meeting 2018, Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018; 78(13 Suppl): Abstract nr 493. doi: 10.1158/1538-7445.AM2018-493
Abaturov, O. E., & Babich, V. L. (2017) Rol mikro-RNK pry zakhvoriuvanniakh biliarnoi systemy [The role of microRNA in diseases of the biliary system]. Zdorov'e rebenka, 7(12), 155–161. doі: 10.22141/2224-0522.214.171.1247.116191 [in Ukrainian].
Li, S. C., Wang, F. S., Yang, Y. L., Tiao, M. M., Chuang, J. H., & Huang, Y. H. (2016) Microarray Study of Pathway Analysis Expression Profile Associated with MicroRNA-29a with Regard to Murine Cholestatic Liver Injuries. Int J Mol Sci., 17(3), 324. doi: 10.3390/ijms17030324
Otsuka, M., Kishikawa, T., Yoshikawa, T., Yamagami, M., Ohno, M., Takata, A., et al. (2016) MicroRNAs and liver disease. J Hum Genet., 62(1), 75–80. doi: 10.1038/jhg.2016.53
Hayes, C. N., & Chayama, K. (2016) MicroRNAs as Biomarkers for Liver Disease and Hepatocellular Carcinoma. Int J Mol Sci., 17(3), 280. doi: 10.3390/ijms17030280
Sakamoto, T., Morishita, А., Nomura, Т., Tani, J., Miyoshi H., Yoneyama, H., et al. (2016) Identification of microRNA profiles associated with refractory primary biliary cirrhosis. Mol Med Rep., 14(4), 3350–6. doi: 10.3892/mmr.2016.5606
How to Cite
LicenseAuthors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)