Genetic polymorphisms in non-alcoholic fatty liver disease

Interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis

L. Carulli, I. Canedi, S. Rondinella, S. Lombardini, D. Ganazzi, S. Fargion, M. De Palma, A. Lonardo, M. Ricchi, M. Bertolotti, N. Carulli, P. Loria

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Abstract

Background: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). Methods: In 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features. Results: IL-6 -174C variant was more prevalent (p <0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p <0.05). The prevalence of IL-6/C variant was higher (83%) in biopsied than in not biopsied subjects (66%) (p <0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p <0.05) compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism was significantly higher in NASH than in NAFLD (p = 0.048). At logistic regression analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics. Conclusions: Our data suggest that IL-6 -174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.

Original languageEnglish
Pages (from-to)823-828
Number of pages6
JournalDigestive and Liver Disease
Volume41
Issue number11
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Genetic Polymorphisms
Fatty Liver
Interleukin-6
Fasting
Insulin
Non-alcoholic Fatty Liver Disease
Differentiation Antigens
Genetic Predisposition to Disease
Plasma Cells
Insulin Resistance
Cell Differentiation
Logistic Models
Alleles
Regression Analysis
Inflammation
Control Groups

Keywords

  • Genes
  • IL-6
  • Inflammation
  • Insulin resistance
  • Steatohepatitis
  • Steatosis

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Genetic polymorphisms in non-alcoholic fatty liver disease : Interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis. / Carulli, L.; Canedi, I.; Rondinella, S.; Lombardini, S.; Ganazzi, D.; Fargion, S.; De Palma, M.; Lonardo, A.; Ricchi, M.; Bertolotti, M.; Carulli, N.; Loria, P.

In: Digestive and Liver Disease, Vol. 41, No. 11, 11.2009, p. 823-828.

Research output: Contribution to journalArticle

Carulli, L, Canedi, I, Rondinella, S, Lombardini, S, Ganazzi, D, Fargion, S, De Palma, M, Lonardo, A, Ricchi, M, Bertolotti, M, Carulli, N & Loria, P 2009, 'Genetic polymorphisms in non-alcoholic fatty liver disease: Interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis', Digestive and Liver Disease, vol. 41, no. 11, pp. 823-828. https://doi.org/10.1016/j.dld.2009.03.005
Carulli, L. ; Canedi, I. ; Rondinella, S. ; Lombardini, S. ; Ganazzi, D. ; Fargion, S. ; De Palma, M. ; Lonardo, A. ; Ricchi, M. ; Bertolotti, M. ; Carulli, N. ; Loria, P. / Genetic polymorphisms in non-alcoholic fatty liver disease : Interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis. In: Digestive and Liver Disease. 2009 ; Vol. 41, No. 11. pp. 823-828.
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abstract = "Background: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). Methods: In 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features. Results: IL-6 -174C variant was more prevalent (p <0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p <0.05). The prevalence of IL-6/C variant was higher (83{\%}) in biopsied than in not biopsied subjects (66{\%}) (p <0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p <0.05) compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism was significantly higher in NASH than in NAFLD (p = 0.048). At logistic regression analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics. Conclusions: Our data suggest that IL-6 -174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.",
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T2 - Interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis

AU - Carulli, L.

AU - Canedi, I.

AU - Rondinella, S.

AU - Lombardini, S.

AU - Ganazzi, D.

AU - Fargion, S.

AU - De Palma, M.

AU - Lonardo, A.

AU - Ricchi, M.

AU - Bertolotti, M.

AU - Carulli, N.

AU - Loria, P.

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N2 - Background: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). Methods: In 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features. Results: IL-6 -174C variant was more prevalent (p <0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p <0.05). The prevalence of IL-6/C variant was higher (83%) in biopsied than in not biopsied subjects (66%) (p <0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p <0.05) compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism was significantly higher in NASH than in NAFLD (p = 0.048). At logistic regression analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics. Conclusions: Our data suggest that IL-6 -174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.

AB - Background: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). Methods: In 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (-174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (-493G/T). In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features. Results: IL-6 -174C variant was more prevalent (p <0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p <0.05). The prevalence of IL-6/C variant was higher (83%) in biopsied than in not biopsied subjects (66%) (p <0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p <0.05) compared than those with G allele. The prevalence of IL-6 -174G/C polymorphism was significantly higher in NASH than in NAFLD (p = 0.048). At logistic regression analysis IL-6 -174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126-15.048) and NASH (OR 7.035, C.I. 1.167-42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics. Conclusions: Our data suggest that IL-6 -174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.

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