Validation of PNPLA3 polymorphisms as risk factor for NAFLD and liver fibrosis in an admixed population

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art_MAZO_Validation_of_PNPLA3_polymorphisms_as_risk_factor_for_2019.PDF (684.38 KB)
Citações na Scopus
40
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER ESPANA
Autores
ALMEIDA, Jazon R.
Citação
ANNALS OF HEPATOLOGY, v.18, n.3, p.466-471, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Introduction and aim: Studies have shown that two polymorphisms were associated with steatosis and progression of non-alcoholic fatty liver disease (NAFLD) in different populations: the Patatin-like Phospholipase Domain Containing 3 (PNPLA3) and Transmembrane 6 Superfamily Member 2 (TM6SF2). However, the frequency and significance of these polymorphisms in an admixed population, i.e., Brazilian, is unknown. Therefore, we aimed to evaluate them in healthy subjects in comparison to patients with NAFLD. Material and methods: This was a multicenter cross-sectional study in 248 patients with biopsy-proven NAFLD and in 134 healthy controls from two tertiary centers in Brazil. PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) polymorphisms were evaluated. Results: In controls, the frequencies of PNPLA3 CC and CG + GG were 49.25% and 50.74%, respectively; in NAFLD patients, this was 31.05% and 68.88% (p = 0.0044, 95% CI 1.037-2.977). PNPLA3 GG subjects had an increased risk (3.29-fold) of having NAFLD when compared to CC subjects (p = 0.0044,95% CI 1.504-7.225). In patients with nonalcoholic steatohepatitis (NASH), PNPLA3 GG compared to CC was associated with higher AST levels [38.4 +/- 25.3 versus 36.7 +/- 40.1 IU/L, p= 0.0395)] and with the presence of liver fibrosis (>= F2 fibrosis, p = 0.0272). TM6SF2 polymorphisms were not in Hardy-Weinberg equilibrium in our NAFLD group precluding further analysis. Conclusion: We demonstrated for the first time that PNPLA3 CG + GG increase the risk of NAFLD among Brazilian subjects. Moreover, PNPLA3 GG was associated with liver enzyme elevation and fibrosis in NASH patients. (C) 2019 Fundacion Clinica Medica Sur, A.C.
Palavras-chave
Non-alcoholic fatty liver disease, Single nucleotide polymorphism, Patatin-like Phospholipase Domain Containing 3, Transmembrane 6 Superfamily Member 2, Nonalcoholic steatohepatitis
URI
https://observatorio.fm.usp.br/handle/OPI/33488
Referências
  1. Anstee QM, 2015, SEMIN LIVER DIS, V35, P270, DOI 10.1055/s-0035-1562947
  2. BasuRay S, 2017, HEPATOLOGY, V66, P1111, DOI 10.1002/hep.29273
  3. Boonvisut S, 2017, LIPIDS HEALTH DIS, V16, DOI 10.1186/s12944-017-0570-y
  4. BOTSTEIN D, 1980, AM J HUM GENET, V32, P314
  5. Bruschi FV, 2017, HEPATOLOGY, V65, P1875, DOI 10.1002/hep.29041
  6. Cavalcante LN, 2015, WORLD J HEPATOL, V7, P1433, DOI 10.4254/wjh.v7.i10.1433
  7. Pontoriero AC, 2015, BMC GENET, V16, DOI 10.1186/s12863-015-0255-3
  8. Chalasani N, 2018, HEPATOLOGY, V67, P328, DOI 10.1002/hep.29367
  9. Chen LZ, 2015, J CLIN TRANSL HEPATO, V3, P265, DOI 10.14218/JCTH.2015.00023
  10. Chung GE, 2018, GUT LIVER, V12, P316, DOI 10.5009/gnl17306
  11. Donati B, 2016, HEPATOLOGY, V63, P787, DOI 10.1002/hep.28370
  12. Dongiovanni P, 2015, BIOMED RES INT, DOI 10.1155/2015/460190
  13. Dongiovanni P, 2015, HEPATOLOGY, V61, P506, DOI 10.1002/hep.27490
  14. Dulai PS, 2017, HEPATOLOGY, V65, P1557, DOI 10.1002/hep.29085
  15. Ehrhardt N, 2017, HUM MOL GENET, V26, P2719, DOI 10.1093/hmg/ddx159
  16. Eslam M, 2018, J HEPATOL, V68, P268, DOI 10.1016/j.jhep.2017.09.003
  17. Grundy SM, 2004, CIRCULATION, V109, P433, DOI 10.1161/01.CIR.0000111245.75752.C6
  18. Huang YC, 2011, J BIOL CHEM, V286, P37085, DOI 10.1074/jbc.M111.290114
  19. Kantartzis K, 2017, DIABETES METAB, V43, P229, DOI 10.1016/j.diabet.2016.11.006
  20. Kawamura Y, 2017, INTERNAL MED, V56, P1459, DOI 10.2169/internalmedicine.56.7830
  21. Kleiner DE, 2005, HEPATOLOGY, V41, P1313, DOI 10.1002/hep.20701
  22. Kovarova M, 2015, J CLIN ENDOCR METAB, V100, pE1568, DOI 10.1210/jc.2015-2978
  23. Kozlitina J, 2014, NAT GENET, V46, P352, DOI 10.1038/ng.2901
  24. Larrieta-Carrasco E, 2018, EXP MOL PATHOL, V104, P50, DOI 10.1016/j.yexmp.2018.01.001
  25. Lins TC, 2010, AM J HUM BIOL, V22, P187, DOI 10.1002/ajhb.20976
  26. Liu YL, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms5309
  27. Mahdessian H, 2014, P NATL ACAD SCI USA, V111, P8913, DOI 10.1073/pnas.1323785111
  28. Marchesini G, 2016, J HEPATOL, V64, P1388, DOI [10.1016/j.jhep.2015.11.004, 10.1007/s00125-016-3902-y]
  29. Martinez LA, 2017, ANN HEPATOL, V16, P909, DOI 10.5604/01.3001.0010.5282
  30. McPherson S, 2017, AM J GASTROENTEROL, V112, P740, DOI 10.1038/ajg.2016.453
  31. Mondul A, 2015, J NUTR, V145, P1687, DOI 10.3945/jn.115.210633
  32. Pingitore P, 2016, HUM MOL GENET, V25, P5212, DOI 10.1093/hmg/ddw341
  33. Pingitore P, 2014, BBA-MOL CELL BIOL L, V1841, P574, DOI 10.1016/j.bbalip.2013.12.006
  34. Pirazzi C, 2014, HUM MOL GENET, V23, P4077, DOI 10.1093/hmg/ddu121
  35. Romeo S, 2008, NAT GENET, V40, P1461, DOI 10.1038/ng.257
  36. Salameh H, 2016, J CLIN TRANSL HEPATO, V4, P175, DOI 10.14218/JCTH.2016.00009
  37. Severson TJ, 2016, WORLD J GASTROENTERO, V22, P6742, DOI 10.3748/wjg.v22.i29.6742
  38. Sookoian S, 2016, SCI REP-UK, V6, DOI 10.1038/srep27718
  39. Sookoian S, 2015, HEPATOLOGY, V61, P515, DOI 10.1002/hep.27556
  40. Sookoian S, 2009, J LIPID RES, V50, P2111, DOI 10.1194/jlr.P900013-JLR200
  41. Trepo E, 2016, J HEPATOL, V65, P399, DOI 10.1016/j.jhep.2016.03.011
  42. Uygun A, 2017, EUR J GASTROEN HEPAT, V29, P441, DOI 10.1097/MEG.0000000000000813
  43. Vasques ACJ, 2008, ARQ BRAS ENDOCRINOL, V52, P32, DOI 10.1590/S0004-27302008000100006
  44. Visscher PM, 2017, AM J HUM GENET, V101, P5, DOI 10.1016/j.ajhg.2017.06.005
  45. Wang XL, 2015, J HEPATOL, V62, P1438, DOI 10.1016/j.jhep.2015.01.040
  46. Wong VWS, 2018, J GASTROEN HEPATOL, V33, P70, DOI 10.1111/jgh.13857
  47. Wood GC, 2017, SCI REP-UK, V7, DOI 10.1038/srep43238
  48. Wood KL, 2015, BMJ OPEN GASTROENTER, V2, DOI 10.1136/bmjgast-2014-000019
  49. Xu RF, 2015, SCI REP-UK, V5, DOI 10.1038/srep09284
  50. Younossi Z, 2018, NAT REV GASTRO HEPAT, V15, P11, DOI 10.1038/nrgastro.2017.109
  51. Younossi ZM, 2016, HEPATOLOGY, V64, P73, DOI 10.1002/hep.28431
  52. Zhang L, 2015, J GASTROEN HEPATOL, V30, P821, DOI 10.1111/jgh.12889

Coleções
Artigos e Materiais de Revistas Científicas - FM/MGT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/07