Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis

Carregando...
Imagem de Miniatura
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2016
Título da Revista
ISSN da Revista
Título do Volume
Editora
BAISHIDENG PUBLISHING GROUP INC
Citação
WORLD JOURNAL OF HEPATOLOGY, v.8, n.24, p.1019-1027, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
AIM To assess lactase gene (LCT)-13910C>T polymorphisms in Brazilian non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients in comparison with healthy controls. METHODS This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clinicas, Sao Paulo, Brazil. The polymorphism of lactase non-persistence/ lactase persistence (LCT-13910C>T) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients (steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher's exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were performed. RESULTS No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients (66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls (59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism (LCT-13910C>T) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase nonpersistence (low lactase activity or hypolactasia) phenotype was associated with higher insulin levels (23.47 +/- 15.94 mu U/mL vs 15.8 +/- 8.33 mu U/mL, P = 0.027) and a higher frequency of insulin resistance (91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes (P = 0.651), dyslipidaemia (P = 0.328), hypertension (P = 0.507) or liver histology in these patients. Moreover, in the NASH patients, hypolactasia was an independent risk factor for insulin resistance even after adjusting for gender and age [OR = 5.0 (95%CI: 1.35-20; P = 0.017)]. CONCLUSION The LCT-13910 genotype distribution in Brazilian NAFLD patients was the same as that of the general population, but hypolactasia increased the risk of insulin resistance in the NASH patients.
Palavras-chave
Lactose intolerance, Genetic polymorphism, Insulin resistance, Non-alcoholic fatty liver disease, Nonalcoholic steatohepatitis
Referências
  1. Almon R, 2007, SCAND J GASTROENTERO, V42, P165, DOI 10.1080/00365520600825257
  2. Almon R, 2010, EUR J NUTR, V49, P141, DOI 10.1007/s00394-009-0058-2
  3. Aune D, 2013, AM J CLIN NUTR, V98, P1066, DOI 10.3945/ajcn.113.059030
  4. Backhed F, 2005, SCIENCE, V307, P1915, DOI 10.1126/science.1104816
  5. Belury MA, 2002, NUTR RES, V22, P817, DOI 10.1016/S0271-5317(02)00393-7
  6. Bettermann K, 2014, INT J MOL SCI, V15, P9924, DOI 10.3390/ijms15069924
  7. Buning C, 2005, DIGESTION, V71, P245, DOI 10.1159/000087050
  8. Calton EK, 2014, NUTR RES, V34, P559, DOI 10.1016/j.nutres.2014.06.012
  9. Chalasani N, 2012, AM J GASTROENTEROL, V107, P811, DOI 10.1038/ajg.2012.128
  10. Corella D, 2011, OBESITY, V19, P1707, DOI 10.1038/oby.2010.320
  11. Crichton GE, 2014, NUTR RES, V34, P1036, DOI 10.1016/j.nutres.2014.04.002
  12. Da Silva MS, 2014, MATURITAS, V77, P221, DOI 10.1016/j.maturitas.2013.12.007
  13. Donovan SM, 2012, ADV NUTR, V3, p450S, DOI 10.3945/an.112.001859
  14. Enattah NS, 2007, AM J HUM GENET, V81, P615, DOI 10.1086/520705
  15. Enattah NS, 2004, EUR J CLIN NUTR, V58, P1319, DOI 10.1038/sj.ejcn.1601971
  16. Enattah NS, 2002, NAT GENET, V30, P233, DOI 10.1038/ng826
  17. Farrell GC, 2006, HEPATOLOGY, V43, pS99, DOI 10.1002/hep.20973
  18. Friedrich DC, 2014, GENET MOL BIOL, V37, P611, DOI [10.1590/S1415-47572014005000012, 10.1590/S1415-47572014000500001]
  19. Gaggini M, 2013, NUTRIENTS, V5, P1544, DOI 10.3390/nu5051544
  20. Grundy SM, 2004, CIRCULATION, V109, P433, DOI 10.1161/01.CIR.0000111245.75752.C6
  21. Hirahatake KM, 2014, METABOLISM, V63, P618, DOI 10.1016/j.metabol.2014.02.009
  22. Hogenauer C, 2005, EUR J GASTROEN HEPAT, V17, P371
  23. Hothorn T, 2006, J COMPUT GRAPH STAT, V15, P651, DOI 10.1198/106186006X133933
  24. Imajo K, 2014, SEMIN IMMUNOPATHOL, V36, P115, DOI 10.1007/s00281-013-0404-6
  25. Ingram CJE, 2009, HUM GENET, V124, P579, DOI 10.1007/s00439-008-0593-6
  26. Jacome-Sosa MM, 2014, J NUTR BIOCHEM, V25, P692, DOI 10.1016/j.jnutbio.2014.02.011
  27. Kalergis Maria, 2013, Front Endocrinol (Lausanne), V4, P90, DOI 10.3389/fendo.2013.00090
  28. Kettunen J, 2010, HUM MOL GENET, V19, P1129, DOI 10.1093/hmg/ddp561
  29. Khabarova Y, 2009, WORLD J GASTROENTERO, V15, P1849, DOI 10.3748/wjg.15.1849
  30. Kleiner DE, 2005, HEPATOLOGY, V41, P1313, DOI 10.1002/hep.20701
  31. Lamri A, 2013, METABOLISM, V62, P1323, DOI 10.1016/j.metabol.2013.04.006
  32. Lerchbaum E, 2012, CLIN ENDOCRINOL, V77, P834, DOI 10.1111/j.1365-2265.2012.04334.x
  33. Madeira IR, 2008, ARQ BRAS ENDOCRINOL, V52, P1466, DOI 10.1590/S0004-27302008000900010
  34. Maga EA, 2012, APPL ENVIRON MICROB, V78, P6153, DOI 10.1128/AEM.00956-12
  35. Martins MLB, 2015, NUTRITION, V31, P716, DOI 10.1016/j.nut.2014.12.017
  36. Mattar R, 2008, CLIN BIOCHEM, V41, P628, DOI 10.1016/j.clinbiochem.2008.01.006
  37. Mattar R, 2012, CLIN EXP GASTROENTER, V5, P113, DOI 10.2147/CEG.S32368
  38. Mattar R, 2009, NUTR J, V8, DOI 10.1186/1475-2891-8-46
  39. MATTHEWS DR, 1985, DIABETOLOGIA, V28, P412, DOI 10.1007/BF00280883
  40. MILLER SA, 1988, NUCLEIC ACIDS RES, V16, P1215, DOI 10.1093/nar/16.3.1215
  41. Miura K, 2014, WORLD J GASTROENTERO, V20, P7381, DOI 10.3748/wjg.v20.i23.7381
  42. Mouzaki M, 2013, HEPATOLOGY, V58, P120, DOI 10.1002/hep.26319
  43. Moya-Camarena SY, 1999, BBA-MOL CELL BIOL L, V1436, P331, DOI 10.1016/S0005-2760(98)00121-0
  44. Mulcare CA, 2004, AM J HUM GENET, V74, P1102, DOI 10.1086/421050
  45. Nagy D, 2011, AM J PHYS ANTHROPOL, V145, P262, DOI 10.1002/ajpa.21490
  46. Nascimbeni F, 2013, J HEPATOL, V59, P859, DOI 10.1016/j.jhep.2013.05.044
  47. Nicklas TA, 2011, AM J CLIN NUTR, V94, P191, DOI 10.3945/ajcn.110.009860
  48. Paolella G, 2014, WORLD J GASTROENTERO, V20, P15518, DOI 10.3748/wjg.v20.i42.15518
  49. Parodi PW, 2016, MED HYPOTHESES, V89, P1, DOI 10.1016/j.mehy.2015.12.028
  50. Peverill W, 2014, INT J MOL SCI, V15, P8591, DOI 10.3390/ijms15058591
  51. Pfeuffer M, 2007, OBES REV, V8, P109, DOI 10.1111/j.1467-789X.2006.00265.x
  52. R Core Team, 2014, R LANG ENV STAT COMP
  53. Samara A, 2013, NUTRITION, V29, P519, DOI 10.1016/j.nut.2012.08.013
  54. Shin H, 2013, J KOREAN MED SCI, V28, P1482, DOI 10.3346/jkms.2013.28.10.1482
  55. Tilg H, 2010, HEPATOLOGY, V52, P1836, DOI 10.1002/hep.24001
  56. Turnbaugh PJ, 2009, NATURE, V457, P480, DOI 10.1038/nature07540
  57. Upton Jeff, 2010, N Z Med J, V123, P123
  58. Vasques ACJ, 2008, ARQ BRAS ENDOCRINOL, V52, P32, DOI 10.1590/S0004-27302008000100006
  59. Vassilatou E, 2014, WORLD J GASTROENTERO, V20, P8351, DOI 10.3748/wjg.v20.i26.8351
  60. Visioli F, 2014, ADV NUTR, V5, P131, DOI 10.3945/an.113.005025
  61. Wang Y, 2012, MOL NUTR FOOD RES, V56, P1234, DOI 10.1002/mnfr.201100517
  62. Wong RJ, 2014, WORLD J HEPATOL, V6, P263, DOI 10.4254/wjh.v6.i5.263
  63. Younossi ZM, 2011, CLIN GASTROENTEROL H, V9, P524, DOI 10.1016/j.cgh.2011.03.020
  64. Zelber-Sagi S, 2009, J HEPATOL, V50, pS375, DOI 10.1016/j.jhep.2010.04.008