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Citation: Raouia ElFihry,  Mohcine Elmessaoudi-Idrissi,  Fatima-Zahra Jadid,  Imane Zaidane,  Hajar Chihab,  Mohamed Tahiri,  Mostafa Kabine,  Wafaa Badre,  Isabelle Chemin,  Agnes Marchio,  Pascal Pineau,  Sayeh Ezzikouri,  Soumaya Benjelloun. Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients [J].VIROLOGICA SINICA.  http://dx.doi.org/10.1007/s12250-020-00220-7

Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients

  • Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including nonalcoholic fatty liver disease (NAFLD), induced by HCV have been shown to accelerate the progression of fibrosis to cirrhosis and to increase the risk of hepatocellular carcinoma. An optimal peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) activity is crucial to prevent NAFLD installation. The present study aims to investigate the associations between two common PPARGC1A polymorphisms (rs8192678 and rs12640088) and the outcomes of HCV infection in a North African context. A series of 592 consecutive Moroccan subjects, including 292 patients with chronic hepatitis C (CHC), 100 resolvers and 200 healthy controls were genotyped using a TaqMan allelic discrimination assay. PPARGC1A variations at rs8192678 and rs12640088 were not associated with spontaneous clearance of HCV infection (adjusted ORs = 0.76 and 0.79 respectively, P >0.05, for both). Furthermore, multivariable logistic regression analysis showed that both SNPs were not associated with fibrosis progression (OR = 0.71; 95% CI 0.20–2.49; P = 0.739; OR = 1.28; 95% CI 0.25–6.54; P = 0.512, respectively). We conclude that, in the genetic context of South Mediterranean patients, rs8192678 and rs12640088 polymorphisms of PPARGC1A are neither associated with spontaneous clearance nor with disease progression in individuals infected with HCV.

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    1. Barroso I, Luan J, Sandhu MS, Franks PW, Crowley V, Schafer AJ, O’Rahilly S, Wareham NJ (2006) Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes. Diabetologia 49:501–505

    2. Burgueno AL, Cabrerizo R, Gonzales Mansilla N, Sookoian S, Pirola CJ (2013) Maternal high-fat intake during pregnancy programs metabolic-syndrome-related phenotypes through liver mitochondrial DNA copy number and transcriptional activity of liver ppargc1a. J Nutr Biochem 24:6–13

    3. Chen Y, Mu P, He S, Tang X, Guo X, Li H, Xu H, Woo SL, Qian X, Zeng L, Wu C (2013) Gly482ser mutation impairs the effects of peroxisome proliferator-activated receptor gamma coactivator-1alpha on decreasing fat deposition and stimulating phosphoenolpyruvate carboxykinase expression in hepatocytes. Nutr Res 33:332–339

    4. Cheng Y, Dharancy S, Malapel M, Desreumaux P (2005) Hepatitis C virus infection down-regulates the expression of peroxisome proliferator-activated receptor alpha and carnitine palmitoyl acyl-CoA transferase 1a. World J Gastroenterol 11:7591–7596

    5. Cheng CF, Ku HC, Lin H (2018) PGC-1alpha as a pivotal factor in lipid and metabolic regulation. Int J Mol Sci 19:3447

    6. Choi J, Ou JH (2006) Mechanisms of liver injury. III. Oxidative stress in the pathogenesis of hepatitis c virus. Am J Physiol Gastrointest Liver Physiol 290:G847–G851

    7. Dharancy S, Malapel M, Perlemuter G, Roskams T, Cheng Y, Dubuquoy L, Podevin P, Conti F, Canva V, Philippe D, Gambiez L, Mathurin P, Paris JC, Schoonjans K, Calmus Y, Pol S, Auwerx J, Desreumaux P (2005) Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. Gastroenterology 128:334–342

    8. Ek J, Andersen G, Urhammer SA, Gaede PH, Drivsholm T, BorchJohnsen K, Hansen T, Pedersen O (2001) Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1(PGC-1) and relationships of identified amino acid polymorphisms to type ii diabetes mellitus. Diabetologia 44:2220–2226

    9. Estall JL, Kahn M, Cooper MP, Fisher FM, Wu MK, Laznik D, Qu L, Cohen DE, Shulman GI, Spiegelman BM (2009) Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression. Diabetes 58:1499–1508

    10. Ezzikouri S, Elfihry R, Chihab H, Elmessaoudi-Idrissi M, Zaidane I, Jadid FZ, Karami A, Tahiri M, Elhabazi A, Kabine M, Chair M, Pineau P, Benjelloun S (2018) Effect of MBOAT7 variant on hepatitis B and C infections in moroccan patients. Sci Rep 8:12247

    11. Finck BN, Kelly DP (2006) PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 116:615–622

    12. Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948

    13. Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, McCaughan GW, George J (2003) Insulin resistance is associated with chronic hepatitis c virus infection and fibrosis progression [corrected]. Gastroenterology 125:1695–1704

    14. Jacobson IM, Cacoub P, Dal Maso L, Harrison SA, Younossi ZM (2010) Manifestations of chronic hepatitis C virus infection beyond the liver. Clin Gastroenterol Hepatol 8:1017–1029

    15. Knobler H, Schattner A (2005) TNF-α, chronic hepatitis c and diabetes: a novel triad. QJM 98:1–6

    16. Kunej T, Globocnik Petrovic M, Dovc P, Peterlin B, Petrovic D (2004) A Gly482Ser polymorphism of the peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) gene is associated with type 2 diabetes in caucasians. Folia Biol (Praha) 50:157–158

    17. Lauer GM, Walker BD (2001) Hepatitis C virus infection. N Engl J Med 345:41–52

    18. Lazo M, Nwankwo C, Daya NR, Thomas DL, Mehta SH, Juraschek S, Willis K, Selvin E (2017) Confluence of epidemics of hepatitis C, diabetes, obesity, and chronic kidney disease in the united states population. Clin Gastroenterol Hepatol 15(1957–1964):e1957

    19. Li X, Monks B, Ge Q, Birnbaum MJ (2007) Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature 447:1012–1016

    20. Liu R, Zhang H, Zhang Y, Li S, Wang X, Wang X, Wang C, Liu B, Zen K, Zhang CY, Zhang C, Ba Y (2017) Peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in hepatocellular carcinoma. Tumour Biol 39:1010428317695031

    21. Maeno T, Okumura A, Ishikawa T, Kato K, Sakakibara F, Sato K, Ayada M, Hotta N, Tagaya T, Fukuzawa Y, Kakumu S (2003)Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol 18:1358–1363

    22. Mirzaei K, Hossein-nezhad A, Emamgholipour S, Ansar H, Khosrofar M, Tootee A, Alatab S (2012) An exonic peroxisome proliferator-activated receptor-gamma coactivator-1alpha variation may mediate the resting energy expenditure through a potential regulatory role on important gene expression in this pathway.

    23. J Nutrigenet Nutrigenomics 5:59–71

    24. Mosley JW, Operskalski EA, Tobler LH, Andrews WW, Phelps B, Dockter J, Giachetti C, Busch MP (2005) Viral and host factors in early hepatitis C virus infection. Hepatology 42:86–92

    25. Musaiger AO (2011) Overweight and obesity in eastern mediterranean region: prevalence and possible causes. J Obes 2011:407237

    26. Niederau C, Lange S, Heintges T, Erhardt A, Buschkamp M, Hurter D, Nawrocki M, Kruska L, Hensel F, Petry W, Haussinger D (1998) Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology 28:1687–1695

    27. Parvaiz F, Manzoor S, Iqbal J, McRae S, Javed F, Ahmed QL, Waris G (2014) Hepatitis C virus nonstructural protein 5a favors upregulation of gluconeogenic and lipogenic gene expression leading towards insulin resistance: a metabolic syndrome. Arch Virol 159:1017–1025

    28. Qadri I, Choudhury M, Rahman SM, Knotts TA, Janssen RC, Schaack J, Iwahashi M, Puljak L, Simon FR, Kilic G, Fitz JG, Friedman JE (2012) Increased phosphoenolpyruvate carboxykinase gene expression and steatosis during hepatitis C virus subgenome replication: role of nonstructural component 5a and CCAAT/

    29. enhancer-binding protein beta. J Biol Chem 287:37340–37351

    30. Ramos-Lopez O, Riezu-Boj JI, Milagro FI, Goni L, Cuervo M, Martinez JA (2018) Association of the Gly482Ser PPARGC1A gene variant with different cholesterol outcomes in response to two energy-restricted diets in subjects with excessive weight.Nutrition 47:83–89

    31. Saremi L, Lotfipanah S, Mohammadi M, Hosseinzadeh H, HosseiniKhah Z, Johari B, Saltanatpour Z (2019) Association between ppargc1a single nucleotide polymorphisms and increased risk of nonalcoholic fatty liver disease among iranian patients with type 2 diabetes mellitus. Turk J Med Sci 49:1089–1094

    32. Shlomai A, Rechtman MM, Burdelova EO, Zilberberg A, Hoffman S, Solar I, Fishman S, Halpern Z, Sklan EH (2012) The metabolic regulator PGC-1alpha links hepatitis C virus infection to hepatic insulin resistance. J Hepatol 57:867–873

    33. Soyal S, Krempler F, Oberkofler H, Patsch W (2006) Pgc-1alpha: a potent transcriptional cofactor involved in the pathogenesis of type 2 diabetes. Diabetologia 49:1477–1488

    34. Tai CM, Huang CK, Tu HP, Hwang JC, Yeh ML, Huang CF, Huang JF, Dai CY, Chuang WL, Yu ML (2016) Interactions of a PPARGC1A variant and a PNPLA3 variant affect nonalcoholic steatohepatitis in severely obese taiwanese patients. Medicine(Baltimore) 95:e3120

    35. Tanaka N, Moriya K, Kiyosawa K, Koike K, Gonzalez FJ, Aoyama T (2008) Pparalpha activation is essential for HCV core proteininduced hepatic steatosis and hepatocellular carcinoma in mice.J Clin Invest 118:683–694

    36. Tazi MA, Abir-Khalil S, Chaouki N, Cherqaoui S, Lahmouz F, Srairi JE, Mahjour J (2003) Prevalence of the main cardiovascular risk factors in Morocco: results of a national survey, 2000. J Hypertens 21:897–903

    37. Thomas DL, Astemborski J, Rai RM, Anania FA, Schaeffer M, Galai N, Nolt K, Nelson KE, Strathdee SA, Johnson L, Laeyendecker O, Boitnott J, Wilson LE, Vlahov D (2000) The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 284:450–456

    38. Villegas R, Williams SM, Gao YT, Long J, Shi J, Cai H, Li H, Chen CC, Tai ES, Consortium A-TD, Hu F, Cai Q, Zheng W, Shu XO (2014) Genetic variation in the peroxisome proliferator-activated receptor (PPAR) and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) gene families and type 2 diabetes.Ann Hum Genet 78:23–32

    39. Vohl MC, Houde A, Lebel S, Hould FS, Marceau P (2005) Effects of the peroxisome proliferator-activated receptor-gamma co-activator-1 Gly482Ser variant on features of the metabolic syndrome. Mol Genet Metab 86:300–306

    40. White DL, Ratziu V, El-Serag HB (2008) Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis. J Hepatol 49:831–844

    41. WHO (2017) Guidelines on hepatitis b and c testing, p 204, Licence:CC BY-NC-SA 3.0 IGO, February 2017 edn Yao W, Cai H, Li X, Li T, Hu L, Peng T (2014) Endoplasmic reticulum stress links hepatitis C virus RNA replication to wildtype PGC-1alpha/liver-specific PGC-1alpha upregulation.J Virol 88:8361–8374

    42. Yoneda M, Hotta K, Nozaki Y, Endo H, Uchiyama T, Mawatari H, Iida H, Kato S, Hosono K, Fujita K, Yoneda K, Takahashi H, Kirikoshi H, Kobayashi N, Inamori M, Abe Y, Kubota K, Saito S, Maeyama S, Wada K, Nakajima A (2008) Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD). BMC Gastroenterol 8:27

    43. Zhang S, Jiang J, Chen Z, Wang Y, Tang W, Chen Y, Liu L (2018)Relationship of PPARG, PPARGC1A, and PPARGC1B polymorphisms with susceptibility to hepatocellular carcinoma in an Eastern Chinese Han population. Onco Targets Ther 11:4651–4660

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    Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients

      Corresponding author: Sayeh Ezzikouri, sayeh.ezzikouri@pasteur.ma
      Corresponding author: Soumaya Benjelloun, soumaya.benjelloun@pasteur.ma
    • 1 Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, 20360 Casablanca, Morocco
    • 2 Laboratoire Santé et Environnement, département de Biologie, Faculté des Sciences Ain Chock, University Hassan II of Casablanca, 20360 Casablanca, Morocco
    • 3 Service d'Hépato-Gastro-Entérologie, CHU Ibn Rochd, 20360 Casablanca, Morocco
    • 4 Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052, CNRS 5286, Lyon Cedex 03, France
    • 5 Unité "Organisation Nucléaire et Oncogenèse", INSERM U993, Institut Pasteur, 75015 Paris, France

    Abstract: Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including nonalcoholic fatty liver disease (NAFLD), induced by HCV have been shown to accelerate the progression of fibrosis to cirrhosis and to increase the risk of hepatocellular carcinoma. An optimal peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) activity is crucial to prevent NAFLD installation. The present study aims to investigate the associations between two common PPARGC1A polymorphisms (rs8192678 and rs12640088) and the outcomes of HCV infection in a North African context. A series of 592 consecutive Moroccan subjects, including 292 patients with chronic hepatitis C (CHC), 100 resolvers and 200 healthy controls were genotyped using a TaqMan allelic discrimination assay. PPARGC1A variations at rs8192678 and rs12640088 were not associated with spontaneous clearance of HCV infection (adjusted ORs = 0.76 and 0.79 respectively, P >0.05, for both). Furthermore, multivariable logistic regression analysis showed that both SNPs were not associated with fibrosis progression (OR = 0.71; 95% CI 0.20–2.49; P = 0.739; OR = 1.28; 95% CI 0.25–6.54; P = 0.512, respectively). We conclude that, in the genetic context of South Mediterranean patients, rs8192678 and rs12640088 polymorphisms of PPARGC1A are neither associated with spontaneous clearance nor with disease progression in individuals infected with HCV.

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