Генетические факторы патогенеза неалкогольной жировой болезни печени: фундаментальные и прикладные аспекты. Есть ли пути решения?

1. Гастроэнтерология. Национальное руководство. Под ред. В.Т.Ивашкина, Т.Л.Лапина. М.: ГЭОТАР-Медиа, 2008; с. 626–32.
2. Chalasani N, Younossi Z, Lavine JE et al. The Diagnosis and Management of Non-Alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012.
3. Torres DM, Williams CD, Harrison SA. Features, Diagnosis, and Treatment of Nonalcoholic Fatty Liver Disease. Gastroenter Hepatol 2012; 10: 837–58.
4. Эпигенетика. Под ред. С.М.Закияна. Новосибирск: Изд-во СО РАН, 2012.
5. Day CP, Daly AK. Academic Publishers, Dordrecht 2001; p. 43–52.
6. Mendez-Sanchez N, Arrese M et al. Liver intern. 2007; 27 (4): 423–33.
7. Browning JD, Szczepaniak LS, Dobbins R et al. Prevalence of hepatic steatosis in an urban population in the United States: impactof ethnicity. Hepatology 2004; 40: 1387–95.
8. Schwimmer JB, Deutsch R, Kahen T et al. Prevalence of fatty liver in children and adolescents. Pediatrics 2006; 118: 1388–93.
9. Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic differences in hepatic steatosis: an insulin resistance paradox? Hepatology 2009; 49: 791–801.
10. Wagenknecht LE, Scherzinger AL, Stamm ER et al. Correlates and heritability of nonalcoholic fatty liver disease in a minority cohort. Obesity (Silver Spring) 2009; 17: 1240–6.
11. Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic differences in hepatic steatosis: an insulin resistance paradox? Hepatology 2009; 49: 791–801.
12. Schwimmer JB, Celedon MA, Lavine JE et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology 2009; 136: 1585–92.
13. Brouwers MC, Cantor RM, Kono N et al. Heritability and genetic loci of fatty liver in familial combined hyperlipidemia. J Lipid Res 2006; 47: 2799–807.
14. Bathum L, Petersen HC, Rosholm JU et al. Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study. Clin Chem 2001; 47: 81–7.
15. Loomba R, Rao F, Zhang L et al. Genetic covariance between gamma-glutamyl transpeptidase and fatty liver risk factors: role of beta2-adrenergic receptor genetic variation in twins. Gastroenterology 2010; 139: 836–45, 45 e1.
16. Jermendy G, Horvath T, Littvay L et al. Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study. Cardiovasc Diabetol 2011; 10: 96.
17. Tarnoki AD, Tarnoki DL, Bata P et al. Heritability of nonalcoholic fatty liver disease and association with abnormal vascular parameters: A twin study. Liver Int 2012; 32: 1287–93.
18. Romeo S, Kozlitina J, Xing C et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461–5.
19. Huang Y, He S, Li JZ et al. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc Natl Acad Sci USA; 107: 7892–7.
20. 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 2009; 285: 6706–15.
21. Kumari M, Schoiswohl G, Chitraju C et al.  Adiponutrin functions as a nutritionally regulated lysophosphatidic Acid acyltransferase. Cell Metab 2012; 15: 691–702.
22. Rotman Y, Koh C, Zmuda JM et al. The association of genetic variability in patatin-like phospholipase domaincontainingpro­tein 3 (PNPLA3) with histological severity of nonalcoholicfatty liver disease. Hepatology 2010; 52: 894–903.
23. 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 2010; 52: 904–12.
24. 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: 1883–94.
25. Valenti L, Alisi A, Nobili V. I148M PNPLA3 variant and progressive liver disease: A new paradigm in hepatology. Hepatology 2012; 56: 1883–9.
26. Zheng Lin, Lv Guo-cai, Sheng Jifang, Yang Yi-da. J Gastroenterol Hepatol 2010; 25: 156–63.
27. Dongiovanni P, Valenti L, Rametta R et al. Gut 2010, 59: 267–73.
28. Oliveira C, Cavaleiro AM. J Gastroenterol Hepatol 2010; 25: 357–61.
29. Loos RJF, Savage DB. Diabetologia 2009, 52: 1000–2.
30. Valenti L,  Motta BM,  Soardo G et al. PNPLA3 I148M Polymorphism, Clinical Presentation, and Survival in Patients with Hepatocellular Carcinoma PLoS One. 2013; 8 (10): e75982. Published online Oct 14, 2013. Doi: 10.1371/journal.pone.0075982 PMCID: PMC3796509.
31. Sookoian S, Pirola CJ. Meta-Analysis of the influence of 1148M variant PNPLA3 on the susceptibility and histological severity on HAFLD. Cell Metab 2012; 15: 691–702.
32. Dongiovanni P, Rametta R, Fracanzani AL et al. Lack of association between peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms and progressive liver damage in patientswith non-alcoholic fatty liver disease: a case control study. BMC Gastroenterol 10: 102.
33. Rey JW, Noetel A, Hardt A et al. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma2 in patients with fatty liver diseases. World J Gastroenterol 16: 5830–7.
34. Gawrieh S, Marion MC, Komorowski R et al. Genetic Variation in the Peroxisome Proliferator Activated Receptor-Gamma Gene Is Associated with Histologically Advanced NAFLD. Dig Dis Sci 2012; 57: 952–7.
35. Reue K. The lipin family: mutations and metabolism. Curr Opin Lipidol 2009; 20: 165–70.
36. Burgdorf KS, Sandholt CH, Sparso T et al. Studies of association between LPIN1 variants and common metabolic phenotypes among 17,538 Danes. Eur J Endocrinol 163: 81–7.
37. Fawcett KA, Grimsey N, Loos RJ et al. Evaluating the role of LPIN1 variation in insulin resistance, body weight, and human lipodystrophy in U.K. Populations. Diabetes 2008; 57: 2527–33.
38. Yao ZM, Vance DE. Head group specificity in the requirement of phosphatidylcholine biosynthesis for very low density lipoprotein secretion from cultured hepatocytes. J Biol Chem 1989; 264:11373–80.
39. Noga AA, Zhao Y, Vance DE. An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins. J Biol Chem 2002; 277: 42358–65.
40. Hebbard L, George J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2011; 8: 35–44.
41. Anstee QM, Goldin RD. Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol 2006; 87: 1–16.
42. Walkey CJ, Yu L, Agellon LB, Vance DE. Biochemical and evolutionary significance of phospholipid methylation. J Biol Chem1998; 273: 27043–6.
43. Song J, da Costa KA, Fischer LM et al. Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD). Faseb J 2005; 19: 1266–71.
44. Dong H, Wang J, Li C et al. The phosphatidylethanolamine Nmethyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population. J Hepatol 2007; 46: 915–20.
45. Valenti L, Fracanzani AL, Bugianesi E et al. HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology 2010; 138: 905–12.
46. Nelson JE, Wilson L, Brunt EM et al. Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease. Hepatology 2011; 53: 448–57.
47. Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease. J Hepatol 2011; 54: 795–809.
48. Paik YH, Schwabe RF, Bataller R et al. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology 2003; 37: 1043–55.
49. Lee JY, Ye J, Gao Z et al. Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. J Biol Chem 2003; 278: 37041–51.
50. Hsu LC, Park JM, Zhang K et al. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 2004; 428: 341–50.
51. Guo J, Loke J, Zheng F et al. Functional linkage of cirrhosispredictive single nucleotide polymorphisms of Toll-like receptor 4 to hepatic stellate cell responses. Hepatology 2009; 49: 960–8.
52. Petta S, Grimaudo S, Camma C et al. IL28B and PNPLA3 polymorphismsaffect histological liver damage in patients with nonalcoholic fatty liver disease. J Hepatol 2012; 56: 1356–62.
53. Dong H, Wang J, Li C et al. The phosphatidylethanolamine Nmethyltransferasegene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population. J Hepatol 2007; 46: 915–20.
54. Mihai D. Niculescu, Corneliu N. Craciunescu et al. Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains. Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, North Carolina, USA, 2007, 2011.
55. Fabbrini E, Mohammed BS, Magkos F et al. Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology 2007; 134: 424–31.
56. Gambino R, Cassader M, Pagano G et al. Polymorphis in microsomal triglyceride transfer protein: a link between liver disease and atherogenic postprandial lipid profile in NASH? Hepatology 2007; 45: 1097–107.
57. Jun DW, Han JH, Jang EC et al. Polymorphisms of microsomal triglyceride transfer protein gene and phosphatidylethanolamine Nmethyltransferase gene in alcoholic and nonalcoholic fatty liver disease in Koreans. Eur J Gastroenterol Hepatol 2009; 21: 667–72.
58. Poly C, Massaro JM, Seshadri S et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort 1–4. Am J Clin Nutr 2011; 94: 1584–91. Printed in USA. 2011 American Society for Nutrition MG.
59. Fischer LM, daCosta KA, Kwock L et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr 2007; 85: 1275–85.
60. Назаренко Л.И., Райхельсон К.Л., Петрова Ю.Н. Значение питания в развитии неалкогольной жировой болезни печени. Вопр. здорового и диетического питания. 2011; 8: 3–9.
61. Назаренко Л.И., Петрова Ю.Н., Райхельсон К.Л., Барановский А.Ю. Ошибки питания пациентов с неалкогольной жировой болезнью печени и пути их коррекции. Клин. и эксперим. гастроэнтерология. 2012; 2: 19–24.
62. Lieber CS et al. Polyenylphosphatidylcholine (PPC) is beneficial for the treatment of hepatitis C patients. Hepatology 2008; 42 (4, Suppl. 1): AASLD Abstracts, 695A.
63. Sas E, Grinevich V, Efimov O. Polyunsaturated Phosphotidilcholine enhances functial liver condition and able to influense positively on liver structure in patient with NAFLD accompanied de diabetes type 2. Results of randomizaed blinded prospective clinical study. J Gastroenterol Barcelona, 18th UEGW, 2010.
64. Sas E, Grinevich V, Efimov O. Prebiotics influence on inflammation level in NAFLD. Hepatology, 68th EASL, 2011.

Л.К.Пальгова

Кафедра гастроэнтерологии и диетологии ГБОУ ВПО Северо-Западный государственный медицинский университет им. И.И.Мечникова Минздрава России, Санкт-Петербург