Клинико-морфологические параллели полиморфизма гена PNPLA3 у пациентов с неалкогольной жировой болезнью печени - Журнал Терапевтический архив №2 Вопросы гастроэнтерологии 2018

Клинико-морфологические параллели полиморфизма гена PNPLA3 у пациентов с неалкогольной жировой болезнью печени

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Аннотация

Неалкогольная жировая болезнь печени (НАЖБП) – наиболее распространенное хроническое заболевание печени; ее выявление в общей популяции достигло глобальных масштабов. Несмотря на то что на ранних стадиях заболевание характеризуется относительно мягким течением, развитие в ходе его естественного течения неалкогольного стеатогепатита, цирроза печени и гепатоцеллюлярной карциномы приводит к ухудшению долгосрочного прогноза. Все больше данных указывает на то, что НАЖБП имеет сложную, многогранную этиологию, включающую множество факторов, в том числе и генетические. В представленном обзоре мы сосредоточились на генетической составляющей НАЖБП, а именно – на роли полиморфизма гена PNPLA3 в развитии и течении заболевания, а также состояний ее прогрессирования, таких как неалкогольный стеатогепатит, цирроз печени и гепатоцеллюлярная карцинома.

Ключевые слова: неалкогольная жировая болезнь печени, неалкогольный стеатогепатит, цирроз печени, PNPLA3.

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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its detection in the general population has reached a global scale. Despite the fact that in the early stages the disease is characterized by a relatively mild period, the development during its natural course of nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma causes deterioration of long-term forecast. Growing evidence indicates that NAFLD is a complex, multifaceted etiology, involving many factors, including genetic. In the present review, we focused on the genetic component of NAFLD, namely, the role of the PNPLA3 gene polymorphism in the development and course of the disease, and States its progression, such as non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma.

Keywords: non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, liver cirrhosis, PNPLA3.

Список литературы

1. De Alwis NMW, Day CP. Non-alcoholic fatty liver disease: Them its gradually clears. J Hepatol. 2008;48:104-12.
2. Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol. 2010;53:372-84.
3. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34:274-85.
4. Miele L, Beale G, Patman G, et al. The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease. Gastroenterology. 2008;35(1):282-91.
5. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40(12):1461-5.
6. Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842-5.
7. Pingitore P, Pirazzi C, Mancina RM, et al. Recombinant PNPLA3 protein shows triglyceride hydrolase activity and its I148M mutation results in loss of function. Biochim Biophys Acta. 2014;1841:574-80.
8. Pirazzi C, Valenti L, Motta BM, et al. PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells. Hum Mol Genet. 2014;23(15):4077-85.
9. Sookoian S, Castaño GO, Burgueño AL, et al. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J Lipid Res. 2009;50(10):2111-6.
10. Valenti L, Al-Serri A, Daly AK, 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):1209-17.
11. Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 Variants Specifically Confer Increased Risk for Histologic Nonalcoholic Fatty Liver Disease But Not Metabolic Disease. Hepatology (Baltimore). 2010;52(3):904-12.
12. Rotman Y, Koh C, Zmuda JM, Kleiner DE, Liang TJ. The Association of Genetic Variability in PNPLA3 with Histological Severity of Non-Alcoholic Fatty Liver Disease. Hepatology (Baltimore). 2010;52(3):894-903.
13. Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology. 2011;53(6):1883-94.
14. Shen JH, Li YL, Li D, Wang NN, Jing L, Huang YH. The rs738409 (I148M) variant of the PNPLA3 gene and cirrhosis: a meta-analysis.
J Lipid Res. 2015;56(1):167-75.
15. Cox AJ, Wing MR, Carr JJ, et al. Association of PNPLA3 SNP rs738409 with liver density in African Americans with type 2 diabetes mellitus. Diabet Metab. 2011;37(5):452-5.
16. Kantartzis K, Peter A, Machicao F, et al. Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes. 2009;58(11):2616-23.
17. Palmer CNA, Maglio C, Pirazzi C, et al. Paradoxical Lower Serum Triglyceride Levels and Higher Type 2 Diabetes Mellitus Susceptibility in Obese Individuals with the PNPLA3 148M Variant. Hennige AM, ed. PLoS ONE. 2012;7(6):e39362.
18. Stojkovic IA, Ericson U, Rukh G, Riddestråle M, Romeo S, Orho-Melander M. The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels. Genes Nutr. 2014;9:200-9.
19. Tang CS, Zhang H, Cheung CY, et al. Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese. Nat Commun. 2015;6:10206.
20. Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, et al. Genome-Wide Association Analysis Identifies Variants Associated withNonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits. PLoS Genet. 2011;7(3):e1001324.
21. Petit JM, Guiu B, Masson D, et al. Specifically PNPLA3-mediated accumulation of liver fat in obese patients with type 2 diabetes. J Clin Endocrinol Metab. 2010;95:430-6.
22. Krawczyk M, Grünhage F, Zimmer V, et al. Variant adiponutrin (PNPLA3) represents a common fibrosis risk gene: Non-invasive elastography-based study in chronic liver disease. J Hepatol. 2011;55: 299-306.
23. Valenti L, Alisi A, Galmozzi E, et al. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology. 2010;52(4):1274-80.
24. Singal AG, Manjunath H, Yopp AC, et al. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis. Review. Am J Gastroenterol. 2014;109(3):325-34.
25. Khlaiphuengsin A, Kiatbumrung R, Payungporn S, et al. Association of PNPLA3 Polymorphism with Hepatocellular Carcinoma Development and Prognosis in Viral and Non-Viral Chronic Liver Diseases. Asian Pac J Cancer Prev. 2015;16(18):8377-82.
26. Abecasis GR, Auton A, Brooks LD, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56-65.
27. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387-95.
28. Browning JD, Kumar KS, Saboorian MH, Thiele DL. Ethnic differences in the prevalence of cryptogenic cirrhosis. Am J Gastroenterol. 2004;99:292-8.
29. Palmer ND, Musani SK, Yerges-Armstrong LM, et al. Characterization of European ancestry nonalcoholic fatty liver disease-associated variants in individuals of African and Hispanic descent. Hepatology. 2013;58:966-75.
30. Qu HQ, Li Q, Grove ML, et al. Population-based risk factors for elevated alanine aminotransferase in a South Texas Mexican-American population. Arch Med Res. 2012;43:482-8.
31. Peng XE, Wu YL, Lin SW, et al. Genetic variants in PNPLA3 and risk of non-alcoholic fatty liver disease in a Han Chinese population. PLoS One. 2012;7:e50256.
32. Li Y, Xing C, Tian Z, Ku HC. Genetic variant I148M in PNPLA3 is associated with the ultrasonography-determined steatosis degree in a Chinese population. BMC Med Genet. 2012;13:113.
33. Kitamoto T, Kitamoto A, Yoneda M, et al. Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan. Hum Genet. 2013;132:783-92.
34. Lee SS, Byoun YS, Jeong SH, et al. Role of the PNPLA3 I148M polymorphism in nonalcoholic fatty liver disease and fibrosis in Korea. Dig Dis Sci. 2014;59:2967-74.
35. Bhatt SP, Nigam P, Misra A, et al. Genetic variation in the patatin-like phospholipase domain-containing protein-3 (PNPLA-3) gene in Asian Indians with nonalcoholic fatty liver disease. Metab Syndr Relat Disord. 2013;11:329-35.
36. Kanth VR, Sasikala M, Rao PN, et al. Pooled genetic analysis in ultrasound measured non-alcoholic fatty liver disease in Indian subjects:
A pilot study. World J Hepatol. 2014;6:435-42.
37. Dubuquoy C, Robichon C, Lasnier F, et al. Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes. J Hepatol. 2011;55:145-53.
38. He S, McPhaul C, Li JZ, et al. A Sequence Variation (I148M) in PNPLA3 Associated with Nonalcoholic Fatty Liver Disease Disrupts Triglyceride Hydrolysis. J Biol Chem. 2010;285(9):6706-15.
39. Smagris E, BasuRay S, Li J, et al. Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis. Hepatology (Baltimore). 2015;61(1):108-18.
40. Pirazzi C, Adiels M, Burza MA, et al. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro. J Hepatol. 2012;57:1276-82.
41. Mondul A, Mancina RM, Merlo A, et al. PNPLA3 I148M variant influences circulating retinol in adults with nonalcoholic fatty liver disease or obesity. J Nutr. 2015;145:1687-91.
42. Kovarova M, Konigsrainer I, Konigsrainer A, et al. The genetic variant I148M in PNPLA3 is associated with increased hepatic retinyl-palmitate storage in humans. J Clin Endocrinol Metab. 2015;100:1568-74.
43. Moreira RK. Hepatic stellate cells and liver fibrosis. Arch Pathol Lab Med. 2007 Nov;131(11):1728-34.

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Авторы

А.С. Тихомирова1, В.А. Кисляков1, И.Е. Байкова1, И.Г. Никитин1,2

1 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
2 ФГАУ «Лечебно-реабилитационный центр» Минздрава России, Москва, Россия

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A. S. Tikhomirova1, V. A. Kislyakov1, I. E. Baykova1, I. G. Nikitin1,2

1 N.I. Pirogov Russian national research medical University, Ministry of health of Russia, Moscow, Russian
2 Higher Medical rehabilitation center, Ministry of health of Russia, Moscow, Russia

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