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Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.

Publication ,  Journal Article
Nelson, JE; Handa, P; Aouizerat, B; Wilson, L; Vemulakonda, LA; Yeh, MM; Kowdley, KV; NASH Clinical Research Network,
Published in: Aliment Pharmacol Ther
December 2016

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). AIM: To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. METHODS: A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. RESULTS: The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. CONCLUSIONS: These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression.

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Published In

Aliment Pharmacol Ther

DOI

EISSN

1365-2036

Publication Date

December 2016

Volume

44

Issue

11-12

Start / End Page

1253 / 1264

Location

England

Related Subject Headings

  • White People
  • Polymorphism, Single Nucleotide
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Logistic Models
  • Liver Cirrhosis
  • Liver
  • Interleukin-6
  • Interleukin-1beta
 

Citation

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MLA
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Nelson, J. E., Handa, P., Aouizerat, B., Wilson, L., Vemulakonda, L. A., Yeh, M. M., … NASH Clinical Research Network, . (2016). Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Aliment Pharmacol Ther, 44(11–12), 1253–1264. https://doi.org/10.1111/apt.13824
Nelson, J. E., P. Handa, B. Aouizerat, L. Wilson, L. A. Vemulakonda, M. M. Yeh, K. V. Kowdley, and K. V. NASH Clinical Research Network. “Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.Aliment Pharmacol Ther 44, no. 11–12 (December 2016): 1253–64. https://doi.org/10.1111/apt.13824.
Nelson JE, Handa P, Aouizerat B, Wilson L, Vemulakonda LA, Yeh MM, et al. Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Aliment Pharmacol Ther. 2016 Dec;44(11–12):1253–64.
Nelson, J. E., et al. “Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.Aliment Pharmacol Ther, vol. 44, no. 11–12, Dec. 2016, pp. 1253–64. Pubmed, doi:10.1111/apt.13824.
Nelson JE, Handa P, Aouizerat B, Wilson L, Vemulakonda LA, Yeh MM, Kowdley KV, NASH Clinical Research Network. Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Aliment Pharmacol Ther. 2016 Dec;44(11–12):1253–1264.
Journal cover image

Published In

Aliment Pharmacol Ther

DOI

EISSN

1365-2036

Publication Date

December 2016

Volume

44

Issue

11-12

Start / End Page

1253 / 1264

Location

England

Related Subject Headings

  • White People
  • Polymorphism, Single Nucleotide
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Logistic Models
  • Liver Cirrhosis
  • Liver
  • Interleukin-6
  • Interleukin-1beta