ROLE OF GENETIC FACTORS IN THE DEVELOPMENT OF METABOLICALLY ASSOCIATED FATTY LIVER DISEASE (LITERATURE REVIEW)

Relevance. Liver diseases are a serious social problem. The study of the pathogenetic mechanisms of the development of these diseases, the search for treatment methods that can radically improve the patient’s condition and stop the development of the disease is very relevant and in demand.

Aim: to conduct a literature review of currently known genetic factors in the etiology of non-alcoholic liver disease.

 Research results. The review presents the genetic aspects of the development of metabolically associated fatty liver disease (new name) or non-alcoholic fatty liver disease (common name). The leading syndromes accompanying the development of the disease are considered: asthenic syndrome, circadian rhythm disturbance syndrome ("circadian" syndrome), obstructive sleep apnea syndrome, cytolysis syndrome, insulin resistance syndrome, metabolic syndrome, pain syndrome, dyspeptic syndrome, irritable bowel syndrome, bacterial overgrowth syndrome growth, hepatomegaly and/or splenomegaly syndrome, fibrosis syndrome, polycystic ovary syndrome. The main comorbid conditions are covered: from the liver - hepatocellular carcinoma, cirrhosis of the liver, extrahepatic complications - obesity, type 2 diabetes mellitus, cardiovascular disorders - atherosclerosis, from the kidneys - chronic renal disease, etc. Data on genes affecting the development of diseases: PNPLA3, TM6SF2, MBOAT7, HSD17B13, GCKR, HFE, CP, INS, PPARG, CYP11A, AR, ENPP1, MTTP.

Conclusion. Studying the etiological causes (genetic polymorphisms) of non-alcoholic fatty liver disease is the main task towards solving the problems of effective patient care.

1. Chiang D.J., McCullough A.J. The impact of obesity and metabolic syndrome on alcoholic liver disease. Clin Liver Dis. 2014;18(1):157-163. DOI:10.1016/j.cld.2013.09.006.

2. Ивашкин В.Т., Драпкина О.М., Шульпекова Ю.О. Диагностика и лечение неалкогольной жировой болезни печени. Методические рекомендации. М.: ООО «Издательский дом «М-Вести»;2009 [Ivashkin V.T., Drapkina O.M., Shulpekova Yu.O. Diagnosis and treatment of non-alcoholic fatty liver disease. Guidelines. M.:«Publishing House «M-Vesti»; 2009 (In Russian)].

3. Драпкина О.М., Ивашкин В.Т. Эпидемиологические особенности неалкогольной жировой болезни печени в России (Результаты открытого многоцентрового проспективного исследования-наблюдения DIREG L 01903). Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2014;4:32-38 [Drapkina O.M., Ivashkin V.T. Epidemiological features of non-alcoholic fatty liver disease in Russia (Results of an open multicenter prospective observational study DIREG L 01903). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2014;4:32-38 (In Russian)]. http://old-gastro-j.ru/files/_2014_4_s4_1417549799.pdf [дата доступа: 10.05.2024].

4. Евстифеева С.Е., Шальнова С.А., Куценко В.А. и др. Распространенность неалкогольной жировой болезни печени среди населения трудоспособного возраста: ассоциации с социально-демографическими показателями и поведенческими факторами риска (данные ЭССЕ-РФ-2). Кардиоваскулярная терапия и профилактика. 2022;21(9):3356 [Evstifeeva S.E., Shalnova S.A., Kutsenko V.A. et al. Prevalence of non-alcoholic fatty liver disease among the working-age population: associations with socio-demographic indicators and behavioral risk factors (ESSE RF-2 data). Cardiovascular Therapy and Prevention. 2022;21(9):3356 (In Russian)]. DOI:10.15829/1728-8800-2022-3356

5. Vernon G., Baranova A., Younossi Z.M. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274-285. DOI:10.1111/j.1365-2036.2011.04724.x

6. Estes C., Anstee Q.M., Arias-Loste M.T. et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. Hepatology. 2018;69:896-904. DOI:10.1016/j.jhep.2018.05.036.

7. Пальгова Л.К., Барановский А.Ю., Ушакова Т.И. и др. Эпидемиологические особенности неалкогольной жировой болезни печени в Cеверо-Западном регионе России (результаты открытого многоцентрового проспективного исследования DIREG 2). Вестник СПбГУ. Медицина. 2017; 12(2):118–135 [Palgova L.K., Baranovsky A.Yu., Ushakova T.I. et al. Epidemiological features of non-alcoholic fatty liver disease in the North-West region of Russia (results of an open multicenter prospective study DIREG 2). Bulletin of St. Petersburg State University. Medicine. 2017;12(2):118–135 (In Russian)]. DOI:10.21638/11701/spbu11.2017.201

8. Мишина Е.Е., Майоров А.Ю., Богомолов П.О. и др. Неалкогольная жировая болезнь печени: причина или следствие инсулинорезистентности? Сахарный диабет. 2017;20(5):335-342 [Mishina E.E., Mayorov A.Y., Bogomolov P.O., Matsievich M.V., Kokina K.Y., Bogolyubova A.V. Nonalcoholic fatty liver disease: cause or consequence of insulin resistance? Diabetes mellitus. 2017;20(5):335-343 (In Russian)]. DOI: 10.14341/DM9372

9. Бутрова С.А., Елисеева А.Ю. Неалкогольная жировая болезнь печени: актуальные проекты. Ожирение и метаболизм. 2007;4(2):2-7 [Butrova S.A., Eliseeva A.Yu. Nealkogol'naya zhirovaya bolezn' pecheni: aktual'nye proekty. Obesity and metabolism. 2007;4(2):2-7 (In Russian)]. DOI:10.14341/2071-8713-5155

10. Елисеева Л. Н., Болотова Е. В. Распространенность неалкогольной жировой болезни печени среди пациентов амбулаторно-поликлинического звена в Краснодаре. Доктор.Ру. 2018;7(151):25–29 [Eliseeva L. N., Bolotova E. V. Incidence of Nonalcoholic Fatty Liver Disease in Outpatient Patients in Krasnodar. Doctor.Ru. 2018; 7(151): 25–29 (In Russian)]. DOI:10.31550/1727-2378-2018-151-7-25-29

11. Драпкина О.М., Буеверов А.О. Неалкогольная жировая болезнь печени как мультидисциплинарная патология. М.: Видокс; 2017 [Drapkina O. M., Bueverov A.O. Nealkogol’naya zhirova-ya bolezn’ pecheni kak mul’tidistciplinarnaya patologiya [Non-alcoholic fatty liver disease as a multidisciplinary pathology]. M.: Vidoks; 2017 (In Russian)].

12. Kelley C.E., Brown A.J., Diehl A.M., Setji T.L. Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J Gastroenterol. 2014;20(39):14172-14184. DOI:10.3748/wjg.v20.i39.14172

13. Диагностика и лечение неалкогольной жировой болезни печени: методические рекомендации для врачей Российского общества по изучению печени. Под ред. Ивашкина В.Т. М.:МЕДпресс-информ;2015 [Diagnosis and treatment of non-alcoholic fatty liver disease: guidelines for doctors of the Russian Society for the Study of the Liver. Ed. Ivashkina V.T. M.: MEDpress-inform; 2015 (In Russian)].

14. Дедов И.И., Бутрова С.А. Синдром поликистозных яичников и метаболический синдром. Ожирение и метаболизм. 2006;3(1):30-40 [Dedov I.I., Butrova S.A. Sindrom polikistoznykh yaichnikov i metabolicheskiy sindrom. Obesity and metabolism. 2006;3(1):30-40 (In Russian)]. DOI:10.14341/2071-8713-4940

15. Cheungpasitporn W., Thongprayoon C., O'Corragain O.A. et al. Associations of sugar-sweetened and artificially sweetened soda with chronic kidney disease: a systematic review and meta-analysis. Nephrology (Carlton). 2014;19(12):791-797. DOI:10.1111/nep.12343.

16. Baguet J.P., Barone-Rochette G., Tamisier R. et al. Mechanisms of cardiac dysfunction in obstructive sleep apnea. Nat Rev Cardiol. 2012;9(12):679-688. DOI:10.1038/nrcardio.2012.141.

17. Parati G., Lombardi C., Hedner J. et al. Position paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European Society of Hypertension, by the European Respiratory Society and by the members of European COST (COoperation in Scientific and Technological research) ACTION B26 on obstructive sleep apnea. J Hypertens. 2012;30(4):633-646. DOI:10.1097/HJH.0b013e328350e53b

18. Eshraghian A., Hamidian Jahromi A. Non-alcoholic fatty liver disease and thyroid dysfunction: a systematic review. World J Gastroenterol. 2014;20(25):8102-8109. DOI:10.3748/wjg.v20.i25.8102

19. Носов А.Е., Зенина М.Т., Горбушина О.Ю. и др. Значимость клинико-лабораторных индексов в диагностике неалкогольной жировой болезни печени. Терапевтический архив. 2021;93(8):883-889 [Nosov A.E., Zenina M.T., Gorbushina O.Yu. et al. Diagnostic significance of clinical and laboratory indices in predicting non-alcoholic fatty liver disease during screening studies. Terapevticheskii Arkhiv (Ter. Arkh.). 2021;93(8):883–889 (In Russian)]. DOI: 10.26442/00403660.2021.08.200973

20. Allen A.M., Therneau T.M., Larson J.J. et al. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study. Hepatology. 2018;67(5):1726-1736. DOI:10.1002/hep.29546.

21. Мишина Е.Е., Майоров А.Ю., Богомолов П.О. и др. Неалкогольная жировая болезнь печени: причина или следствие инсулинорезистентности? Сахарный диабет. 2017;20(5):335-343 [Mishina E.E., Mayorov A.Y., Bogomolov P.O. et al. Nonalcoholic fatty liver disease: cause or consequence of insulin resistance? Diabetes mellitus. 2017;20(5):335-343 (In Russian)]. DOI:10.14341/DM9372

22. Rubin D., Helwig U., Pfeuffer M. et al. A common functional exon polymorphism in the microsomal triglyceride transfer protein gene is associated with type 2 diabetes, impaired glucose metabolism and insulin levels. J Hum Genet. 2006;51(6):567-574. DOI:10.1007/s10038-006-0400-y.

23. Das K., Chowdhury A. Lean NASH: distinctiveness and clinical implication. Hepatol Int. 2013;7 Suppl 2:806-813. DOI:10.1007/s12072-013-9477-5.

24. Вахрушев Я.М., Лукашевич А.П. Значение синдрома избыточного бактериального роста в нарушении метаболических функций печени при неалкогольной жировой болезни печени. Терапевтический архив. 2021;93(2): 169-173 [Vakhrushev, Y. M., & Lukashevich, A. P. (2021). The importance of the bacterial overgrowth syndrome in the development of disorders metabolic functions of the liver in non-alcoholic fatty liver disease. Terapevticheskii Arkhiv, 93(2), 169-173 (In Russian)]. DOI:10.26442/00403660.2021.02.200622

25. Селиверстов П.В., Джадхав С.Н., Цурцумия Д.Б. и др. Неалкогольная жировая болезнь печени: возможности диагностики. РМЖ. 2019;5:36–40 [: Seliverstov P.V., Dzhadkhav S.N., Tsurtsumia D.B. et al. Diagnostic capabilities in non-alcoholic fatty liver disease. RMJ. 2019;5:36–40 (In Russian)]. https://www.rusmedreview.com/upload/iblock/c0e/36-40.pdf [дата доступа: 10.05.2024].

26. Успенская Ю.Б., Кузнецова И.В., Ведзижева Э.Р. Неалкогольная жировая болезнь печени у пациенток с синдромом поликистозных яичников. Consilium Medicum. 2016;18(6):52–58 [Uspenskaya Yu.B., Kuznetsova I.V., Vedzizheva E.R. Nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Consilium Medicum. 2016;18(6):52–58 (In Russian)]. DOI:10.26442/2075-1753_2016.6.52-58

27. Ливзан М.А., Гаус О.В., Николаев Н.А., Кролевец Т.С. НАЖБП: коморбидность и ассоциированные заболевания. Экспериментальная и клиническая гастроэнтерология. 2019;170(10):57–65 [Livzan M.A., Gaus O.V., Nikolaev N.A., Krolevetz T.S. NAFLD: comorbidity and associated diseases. Experimental and Clinical Gastroenterology. 2019;1(10):57-65 (In Russian)]. DOI:10.31146/1682-8658-ecg-170-10-57-65

28. Драпкина О.М., Яфарова А.А. Неалкогольная жировая болезнь печени и сердечно-сосудистый риск: состояние проблемы. Рациональная фармакотерапия в кардиологии. 2017;13(5):645–650 [Drapkina O.M., Yafarova A.A. Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk: Scientific Problem State. Rational Pharmacotherapy in Cardiology 2017;13(5):645-650 (In Russian)]. DOI:10.20996/1819-6446-2017-13-5-645-650

29. Fraser A., Harris R., Sattar N. et al. Gamma-glutamyltransferase is associated with incident vascular events independently of alcohol intake: analysis of the British Women's Heart and Health Study and Meta-Analysis. Arterioscler Thromb Vasc Biol. 2007;27(12):2729-2735. DOI:10.1161/ATVBAHA.107.152298.

30. Ballestri S, Lonardo A, Bonapace S, Byrne CD, Loria P, Targher G. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20(7):1724-1745. DOI:10.3748/wjg.v20.i7.1724.

31. Руженцова Т.А. Кардиомиопатии у детей. Медицинский совет. 2014;(6):66-69 [Ruzhentsova TA. Сardiomyopathy in children. Meditsinskiy sovet = Medical Council. 2014;(6):66-69 (In Russian)]. DOI:10.21518/2079-701X-2014-6-66-69.

32. Portillo-Sanchez P., Bril F., Maximos M. et al. High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. J Clin Endocrinol Metab. 2015;100(6):2231-2238. DOI:10.1210/jc.2015-1966.

33. Rinella M.E. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-2273. DOI:10.1001/jama.2015.5370.

34. Ryu S., Chang Y., Jung H.S. et al. Relationship of sitting time and physical activity with non-alcoholic fatty liver disease. J Hepatol. 2015;63(5):1229-1237. DOI:10.1016/j.jhep.2015.07.010.

35. Rinella M.E. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-2273. DOI:10.1001/jama.2015.5370

36. Eshraghian A., Hamidian Jahromi A. Non-alcoholic fatty liver disease and thyroid dysfunction: a systematic review. World J Gastroenterol. 2014;20(25):8102-8109. DOI:10.3748/wjg.v20.i25.8102

37. Pagadala M.R., Zein C.O., Dasarathy S. et al. Prevalence of hypothyroidism in nonalcoholic fatty liver disease. Dig Dis Sci. 2012;57(2):528-534. DOI:10.1007/s10620-011-2006-2.

38. Cheungpasitporn W., Thongprayoon C., O'Corragain O.A. et al. Associations of sugar-sweetened and artificially sweetened soda with chronic kidney disease: a systematic review and meta-analysis. Nephrology (Carlton). 2014;19(12):791-797. DOI:10.1111/nep.12343.

39. Pacifico L., Bonci E., Andreoli G.M. et al. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity. Int J Mol Sci. 2016;17(8):1218. DOI:10.3390/ijms17081218

40. Aron-Wisnewsky J., Minville C., Tordjman J. et al. Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol. 2012;56(1):225-233. DOI:10.1016/j.jhep.2011.04.022.

41. Musso G., Gambino R., Tabibian J.H. et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014;11(7):e1001680. DOI:10.1371/journal.pmed.1001680.

42. Targher G., Lonardo A., Rossini M. Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link?. J Endocrinol Invest. 2015;38(8):817-825. DOI:10.1007/s40618-015-0315-6

43. Jinjuvadia R., Lohia P., Jinjuvadia C. et al. The association between metabolic syndrome and colorectal neoplasm: systemic review and meta-analysis. J Clin Gastroenterol. 2013;47(1):33-44. DOI:10.1097/MCG.0b013e3182688c15.

44. Miele L., Vallone S., Cefalo C. et al. Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51(4):778-786. DOI:10.1016/j.jhep.2009.06.008.

45. Gisondi P., Targher G., Zoppini G., Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51(4):758-764. DOI:10.1016/j.jhep.2009.04.020.

46. Ливзан М.А., Кролевец Т.С., Лаптева И.В., Черкащенко Н.А. Неалкогольная жировая болезнь печени у лиц с абдоминальным типом ожирения. Доказательная гастроэнтерология. 2014;3(4):8 14 [Livzan M.A., Korolevets T.S., Lapteva I.V., Cherkashchenko N.A. Non-alcoholic fatty liver disease in the patients presenting with abdominal obesity. Russian Journal of Evidence-Based Gastroenterology. 2014;3(4):8 14 (In Russian)]. DOI:10.17116/dokgastro2014348-14

47. Кондратова М.А., Куимов А.Д., Максимов В.Н. и др. Мутации в гене HFE у больных неалкогольной жировой болезнью печени, особенности обменных нарушений. Экспериментальная и клиническая гастроэнтерология. 2017;145(09):18-24 [Kondratova M.A., Kuimov A.D., Maksimov V.N. et al. The frequency of HFE gene polymorphism in patients with nonalcoholic liver disease and in persons of the general population, features of metabolic disorders. Experimental and Clinical Gastroenterology Journal. 2017;145(09):18-24 (In Russian)]. http://gastrossr.org/index.php/en/2017e/e09-145 [дата доступа: 10.05.2024].

48. Богомолов П.О., Кокина К.Ю., Майоров А.Ю., Мишина Е.Е. Генетические аспекты неалкогольной жировой болезни печени. Вопросы современной педиатрии. 2018;17(6):442–448 [Bogomolov P.O., Kokina K.Yu., Mayorov A.Yu., Mishina E.E. Genetic Aspects of Non-Alcoholic Fatty Liver Disease. Current Pediatrics. 2018;17(6):442-448 (In Russian)]. DOI: 10.15690/vsp.v17i6.1974

49. Speliotes E.K., Yerges-Armstrong L.M., Wu J. et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7(3):e1001324. DOI:10.1371/journal.pgen.1001324

50. Бурдули А.Г., Файзуллин Л.З., Васильев Е.В. и др. Полиморфизм гена андрогенового рецептора и минеральная плотность костной ткани у женщин с аменореей. Доктор.Ру. 2012;1(69):24-27 [Burduli A.G., Faizullin L.Z., Vasiliev E.V. et al. Androgen Receptor Gene Polymorphism and Bone Mineral Density in Women with Amenorrhea. Doctor.Ru. 2012;1(69):24-27 (In Russian)]. https://cyberleninka.ru/article/n/polimorfizm-gena-androgenovogo-retseptora-i-mineralnaya-plotnost-kostnoy-tkani-u-zhenschin-s-amenoreey [дата доступа: 10.05.2024].

51. Киселева Е.В., Демидова Т.Ю. Неалкогольная жировая болезнь печени и сахарный диабет 2 типа: проблема сопряженности и этапности развития. Ожирение и метаболизм. 2021;18(3):313-319 [Kiseleva E.V., Demidova T.Y. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the problem of conjunction and phasing. Obesity and metabolism. 2021;18(3):313-319 (In Russian)]. DOI:10.14341/omet12758

52. Petta S., Miele L., Bugianesi E. et al. Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease. PLoS One. 2014;9(2):e87523. DOI:10.1371/journal.pone.0087523.

53. Makkonen J., Pietilainen K.H., Rissanen A. et al. Genetic factors contribute to variation in serum alanine aminotransferase activity independent of obesity and alcohol: a study in monozygotic and dizygotic twins. J Hepatol. 2009;50(5):1035–1042. DOI: 10.1016/ j.jhep.2008.12.025.

54. Guerrero R., Vega G.L., Grundy S.M. et al. Ethnic differences in hepatic steatosis: an insulin resistance paradox. Hepatology. 2009; 49(3):791–801. DOI: 10.1002/hep.22726.

55. Valenti L., Al-Serri A., Daly A.K. et al. Homozygosity, for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2010;51(4):1209–1217. DOI: 10.1002/hep.23622.

56. Basantani M.K., Sitnick M.T., Cai L. et al. Pnpla3/Adiponutrin defi-ciency in mice does not contribute to fatty liver disease or meta-bolic syndrome. Lipid Res. 2011;52(2):318–329. DOI: 10.1194/ jlr.M011205.

57. Kumari M., Schoiswohl G., Chitraju C. et al. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab. 2012;15(5):691–702. DOI: 10.1016/j.cmet.2012.04.008.

58. Chen W., Chang B., Li L., Chan L. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology. 2010;52(3):1134–1142. DOI: 10.1002/hep.23812.

59. Bruschi F.V., Claudel T., Tardelli M. et al. The PNPLA3 I148M variant modulates the fibrogenic phenotype of human hepatic stellate cells. Hepatology. 2017;65(6):1875–1890. DOI: 10.1002/hep.29041.

60. Valenti L., Rumi M., Galmozzi E. et al. Patatin-like phospholi-pase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C. Hepatology. 2011;53(3):791–799. DOI: 10.1002/hep.24123.

61. Kozlitina J., Smagris E., Stender S. et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014;46:352–356. DOI:10.1038/ng.2901

62. Petta S., Miele L., Bugianesi E. et al. Glucokinase regulatory protein gene polymorphism affects liver fibrosis in nonalcoholic fatty liver disease. PLoS One. 2014;9(2):e87523. DOI: 10.1371/journal. pone.0087523.

63. Mahdessian H, Taxiarchis A, Popov S, et al. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content. Proc Natl Acad Sci U S A. 2014;111(24):8913-8918. DOI:10.1073/pnas.1323785111.

64. Liu Y.L., Reeves H.L., Burt A.D. et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with nonalcoholic fatty liver disease. Nat Commun. 2014;5:4309. DOI:10.1038/ncomms5309.

65. Milano M., Aghemo A., Mancina R.M. et al. Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients. Hepatology. 2015;62(1):111–117. DOI:10.1002/hep.27811

66. Speliotes E.K., Yerges-Armstrong L.M., Wu J. et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7(3):e1001324. DOI: 10.1371/journal.pgen.1001324

67. Beer N.L., Tribble N.D., McCulloch L.J. et al. The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver. Hum Mol Genet. 2009;18(21):4081–4088. DOI:10.1093/hmg/ddp357.

68. Santoro N., Zhang C.K., Zhao H. et al. Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents. Hepatology. 2012;55(3):781–789. DOI:10.1002/hep.24806.

69. Пальцев И.В., Калинин А.Л. Мутации гена HFE как фактор риска развития гемохроматоза у больных хроническими диффузными заболеваниями печени. Проблемы здоровья и экологии. 2010;(4):53-57 [Paltsev I.V., Kalinin A.L. M utations of gene HFE as a risk factor of hemochromatosis development at patient with chronic diffuse liver diseases. Health and Ecology Issues. 2010;(4):53-57 (In Russian)]. DOI:10.51523/2708-6011.2010-7-4-10

70. Смирнова О.В., Лагутинская Д.В. Полиморфизмы генов HSD17B13, GCKR, HFE и CP как факторы развития неалкогольной жировой болезни печени и сопутствующих ее заболеваний. Медицинский Совет. 2023;(8):119-125 [Smirnova O.V., Lagutinskaya D.V. Polymorphisms of HSD17B13, GCKR, HFE, and CP as factors of the development of non-alcoholic fatty liver disease and comorbid diseases. Meditsinskiy sovet = Medical Council. 2023;(8):119-125 (In Russian)]. DOI:10.21518/ms2022-026.

71. Ахмедов В.А., Меликов Т.И. Генетические аспекты формирования неалкогольной жировой болезни печени. Лечащий врач. 2019;8:28-31 [Akhmedov V.A., Melikov T.I. Genetic aspects of the formation of non-alcoholic fatty liver disease. Lechashchiy vrach. 2019;8:28-31 (In Russian)]. DOI:10.26295/OS.2019.70.74.004

72. Шулькина С.Г., Эрбес П.Э., Смирнова Е.Н. Значение полиморфизма генов ММР12 (rs652483) И PPARG (rs1801282) в формировании неалкогольной жировой болезни печени у женщин с ожирением. Терапия. 2022;10:79-88 [Shulkina S.G., Erbes P.E., Smirnova E.N. The significance of polymorphism of the MMP12 (rs652483) and PPARG (rs1801282) genes in the formation of non-alcoholic fatty liver disease in obese women. Therapy. 2022;10:79-88 (In Russian)]. DOI:10.18565/therapy.2022.10.79-88

73. Королева Е.И., Назаров В.Д., Лапин С.В. и др. Генетические аспекты неклассической формы врожденной гиперплазии коры надпочечников: литературный обзор и собственный опыт. Молекулярная медицина. 2020;18(3):11–19 [Koroleva E.I., Nazarov V.D., Lapin S.V. et al. Genetic aspects of the non-classical form of congenital adrenal hyperplasia: literature review and personal experience. Molecular medicine. 2020;18(3):11–19 (In Russian)]. DOI:10.29296/24999490-2020-03-02

74. Carmina E., Dewailly D., Escobar-Morreale H.F. et al. Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women. Hum Reprod Update. 2017;23(5):580-599. DOI:10.1093/humupd/dmx014.

75. Беглова А.Ю., Елгина С.И., Гордеева Л.А. Полиморфизм генов CYP11A1, CYP17, CYP19 у женщин репродуктивного возраста с синдромом поликистозных яичников. Акушерство и гинекология. 2019;12:148-153 [Beglova A.Yu., Elgina S.I., Gordeeva L.A Polymorphism of the CYP11A1, CYP17A1, and CYP19A1 genes in reproductive-aged women with polycystic ovary syndrome. Obstetrics and Gynegology. 2019;12:148-153 (In Russian)]. DOI:10.18565/aig.2019.12.148-153

76. Pizzuti A., Frittitta L., Argiolas A. et al. A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. Diabetes. 1999;48(9):1881-1884. DOI:10.2337/diabetes.48.9.1881.

77. Böttcher Y., Körner A., Reinehr T. et al. ENPP1 variants and haplotypes predispose to early onset obesity and impaired glucose and insulin metabolism in German obese children. J Clin Endocrinol Metab. 2006;91(12):4948-52. DOI: 10.1210/jc.2006-0540.

78. Cuchel M., Bloedon L.T., Szapary P.O. et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007; 11;356(2):148-56. DOI:10.1056/NEJMoa061189.

79. Al-Shali K., Wang J., Rosen F., Hegele R.A. Ileal adenocarcinoma in a mild phenotype of abetalipoproteinemia. Clin Genet. 2003;63(2):135-8. DOI: 10.1046/j.0009-9163.2002.00175.x.