Apolipoprotein E Polymorphism and Lipid Metabolism Disorders in Children with Cholelithiasis

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Ye.V. Shutova


Relevance. The incidence of cholelithiasis in children in Ukraine has increased from 0.1–1 to 4.8 % in the structure of biliary pathology [6, 9, 13]. Rising the incidence of cholelithiasis in childhood is obvious, but the reasons are not clear. The genetic factors of this disease in childhood are underinvestigated. Objective: to study the associations of apolipoprotein (Apo) E subclasses and parameters of lipid spectrum in children with cholelithiasis. Materials and methods. 44 children (24 girls and 20 boys) with cholelithiasis aged 5–18 years were under supervision. The study involved patients with stage I (n = 23) and stage II (n = 21) cholelithiasis. Genotyping has been performed by Apo E alleles using polymerase chain reaction me­thod (Termocycler test system). Lipid profile has been assessed in different Apo E phenotypes. The findings were statistically processed using STATISTICA 6.0 software package. Results. It has been found that low-density lipoprotein level was significantly different in E3/E4 and E4/E4 phenotypes (pk-w < 0.01). Very-low-density lipoprotein levels differed most significantly in E3/E3 and E3/E4 phenotypes ­(pk-w = 0.02). So, very-low-density lipoprotein values in E3/E4 phenotype were significantly higher than in E3/E3 phenotype (0.89 ± 0.12 mmol/l versus 0.36 ± 0.06 mmol/l, pu < 0.05). In patients with E4/E4 phenotype, atherogenic index was significantly higher (3.45 ±  0.34 c.u.) than in E3/E3 phenotype (2.17 ± 0.12 c.u., pu < 0.05) and E3/E4 phenotype (1.84 ± 0.24 c.u., pu < 0.05). Conclusion. Analysis of lipid spectrum in children with cholelithiasis and different Apo Е phenotypes gives an indication of genetic susceptibility to lipid metabolism disorders. Marker of increased risk for cholelithiasis development is E4/E4 phenotype.

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Shutova, Y. “Apolipoprotein E Polymorphism and Lipid Metabolism Disorders in Children With Cholelithiasis”. CHILD`S HEALTH, no., Oct. 2016, pp. 101-6, doi:10.22141/2224-0551.
Clinical Pediatrics


Hoida SM. [Trends in the prevalence of gallstone disease among the population of Ukraine]. Ukrainskyi medychnyi chasopys. 2011;84(4):111-13. Ukrainian.

Skvorcova THe, Sitkin SI, Radchenko VG, Seliverstov PV, Tkachenko EI. [ Cholelithiasis. Current approaches to diagnosis , treatment and prevention ]. Moscow: Forte print; 2013. 32p. Russian.

Pavlenko MA, Bayramukova AA, Alibaeva NT, Dronov DA, Mirrahimov JeM. [The role of apolipoprotein E gene polymorphism in the development of atherosclerosis ( review)]. Vestnik Kyrgyzsko-Rossiyskogo Slavyanskogo universiteta. 2007;7(9):28-31. Russian.

Tyuryumin YaL, Shanturov VA, Tyuryumina EE. [Physiology of cholesterol metabolism (the review)]. Bulletin of the East Siberian Scientific Center SBRAMS. 2012;84(2 Pt 1):153-8. Russian.

[Unified clinical protocols of medical care for children with diseases of the digestive system] [Internet] Kiev: The Ministry of Health Ukraine; the order N 59 2013 Jan 29 [cited 2016 Jul 9]. Available from: http://www.moz.gov.ua/docfiles/dod59_2_2013.pdf. Ukrainian.

Shutova EV. [Modern ways of improving the diagnosis, prevention , pathogenetic correction of cholesterol cholelithiasis in childhood ]. Sovremennaya pediatriya. 2012; 41(1):110-3. Ukrainian.

Rahilly-Tierney CR, Arnett DK, North KE, Pankow JS, Hunt SC, Ellison RC, Gaziano JM, Djoussé L. Apolipoprotein ε4 polymorphism does not modify the association between body mass index and high-density lipoprotein cholesterol: a cross-sectional cohort study. Lipids Health Dis. 2011 Sep 23;10:167. doi:10.1186/1476-511X-10-167. PubMed PMID: 21939561; PubMed Central PMCID: PMC3187732.

Espinosa-Saavedra D, Flores-Calderón J, González-Ortiz B, Rodríguez-González P. [Characteristics of pediatric patients with biliary lithiasis. Immediate post-operative evolution]. Rev Med Inst Mex Seguro Soc. 2014;52 Suppl 2:S74-7. Spanish. PubMed PMID: 24983561.

Nissinen MJ, Pakarinen MP, Gylling H, Koivusalo A. Cholesterol and non-cholesterol sterols in serum and gallstones interfere with pathogenesis of pediatric gallstone disease: poster presentations 1310: Abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases: the Liver Meeting 2013, November 1-2, 2013, Washington, D.C., USA. Hepatology. 2013; 58(4 Suppl. 1):844A.

Internal Clinical Guidelines Team (UK). Gallstone Disease: Diagnosis and Management of Cholelithiasis, Cholecystitis and Choledocholithiasis. London: National Institute for Health and Care Excellence (UK); 2014 Oct. (NICE Clinical Guidelines, No. 188.) Available from: http://www.ncbi.nlm.nih.gov/books/NBK258747/

Marschall HU, Katsika D, Rudling M, Einarsson C. The genetic background of gallstone formation: an update. Biochem Biophys Res Commun. 2010 May 21;396(1):58-62. doi: 10.1016/j.bbrc.2010.02.143. Review. PubMed PMID: 20494111.

Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver. 2012 Apr;6(2):172-87. doi: 10.5009/gnl.2012.6.2.172. Epub 2012 Apr 17. PubMed PMID: 22570746; PubMed Central PMCID: PMC3343155.

Svensson J, Makin E. Gallstone disease in children. Semin Pediatr Surg. 2012 Aug;21(3):255-65. doi: 10.1053/j.sempedsurg.2012.05.008. Review. PubMed PMID: 22800978.

Jolliffe CJ, Janssen I. Development of age-specific adolescent metabolic syndrome criteria that are linked to the Adult Treatment Panel III and International Diabetes Federation criteria. J Am Coll Cardiol. 2007 Feb 27;49(8):891-8. Epub 2007 Feb 9. PubMed PMID: 17320748.

Banim PJ, Luben RN, Bulluck H, Sharp SJ, Wareham NJ, Khaw KT, Hart AR. The aetiology of symptomatic gallstones quantification of the effects of obesity, alcohol and serum lipids on risk. Epidemiological and biomarker data from a UK prospective cohort study (EPIC-Norfolk). Eur J Gastroenterol Hepatol. 2011 Aug;23(8):733-40. doi: 10.1097/MEG.0b013e3283477cc9. PubMed PMID: 21623190.

Gacenko VP, At'kova ER, Ivanchenkova RA. [The feasibility of an integrated approach for the correction of lipid abnormalities in patients with cholelithiasis and gallbladder cholesterosis ]. Lechashij vrach. 2011;(7):15-9.

Yoo EH, Lee SY. The prevalence and risk factors for gallstone disease. Clin Chem Lab Med. 2009;47(7):795-807. doi: 10.1515/CCLM.2009.194. Review. PubMed PMID: 19499973.

Sherbinina M.B. [Gallstone disease : therapeutic aspects]. Kiev: Medkniga; 2012. 223p. Ukrainian.

European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. J Hepatol. 2016 Jul;65(1):146-81. doi: 10.1016/j.jhep.2016.03.005. Epub 2016 Apr 13. PubMed PMID: 27085810.

Shadrin OG, Shutova EV. [Evaluation of indicators of АPO-АI, АPO-В, АPO-Е apolipoproteins and their correlation with phenotype АPO-Е in children with cholelithiasis]. East European Scientific Journal. 2015;(4 Pt 1):149-153.