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

the NASH Clinical Research Network

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1253-1264
Number of pages12
JournalAlimentary Pharmacology and Therapeutics
Volume44
Issue number11-12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Fatty Liver
Interleukin-6
Mallory Bodies
Fibrosis
Alleles
Interleukin-1
Genotype
Non-alcoholic Fatty Liver Disease
Genes
Single Nucleotide Polymorphism
Life Style
Obesity
Logistic Models
Cytokines
Diet
Inflammation
Biopsy
Liver

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. / the NASH Clinical Research Network.

In: Alimentary Pharmacology and Therapeutics, Vol. 44, No. 11-12, 01.12.2016, p. 1253-1264.

Research output: Contribution to journalArticle

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title = "Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms",
abstract = "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.",
author = "{the NASH Clinical Research Network} and Nelson, {J. E.} and P. Handa and B. Aouizerat and L. Wilson and Vemulakonda, {L. A.} and Yeh, {M. M.} and Kowdley, {K. V.} and Abrams, {Stephanie H.} and Ryan Himes and Rajesh Krisnamurthy and Leanel Maldonado and Patricia Brandt and Srinivasan Dasarathy and Jaividhya Dasarathy and Carol Hawkins and McCullough, {Arthur J.} and Srinivasan Dasarathy and McCullough, {Arthur J.} and Mangesh Pagadala and Rish Pai and Ruth Sargent and Shetal Shah and Claudia Zein and Kimberlee Bernstein and Kim Cecil and Stephanie DeVore and Rohit Kohli and Kathleen Lake and Daniel Podberesky and Crystal Slaughter and Stavra Xanthakos and Gerald Behr and Lavine, {Joel E.} and Ali Mencin and Nadia Ovchinsky and Elena Reynoso and Abdelmalek, {Manal F.} and Mustafa Bashir and Stephanie Buie and Diehl, {Anna Mae} and Cynthia Guy and Christopher Kigongo and Pan, {Yi Ping} and Naga Chalasani and Oscar Cummings and Marwan Ghabril and Jean Molleston and Kumar Sandrasegaran and Girish Subbarao and Raj Vuppalanchi",
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T1 - Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms

AU - the NASH Clinical Research Network

AU - Nelson, J. E.

AU - Handa, P.

AU - Aouizerat, B.

AU - Wilson, L.

AU - Vemulakonda, L. A.

AU - Yeh, M. M.

AU - Kowdley, K. V.

AU - Abrams, Stephanie H.

AU - Himes, Ryan

AU - Krisnamurthy, Rajesh

AU - Maldonado, Leanel

AU - Brandt, Patricia

AU - Dasarathy, Srinivasan

AU - Dasarathy, Jaividhya

AU - Hawkins, Carol

AU - McCullough, Arthur J.

AU - Dasarathy, Srinivasan

AU - McCullough, Arthur J.

AU - Pagadala, Mangesh

AU - Pai, Rish

AU - Sargent, Ruth

AU - Shah, Shetal

AU - Zein, Claudia

AU - Bernstein, Kimberlee

AU - Cecil, Kim

AU - DeVore, Stephanie

AU - Kohli, Rohit

AU - Lake, Kathleen

AU - Podberesky, Daniel

AU - Slaughter, Crystal

AU - Xanthakos, Stavra

AU - Behr, Gerald

AU - Lavine, Joel E.

AU - Mencin, Ali

AU - Ovchinsky, Nadia

AU - Reynoso, Elena

AU - Abdelmalek, Manal F.

AU - Bashir, Mustafa

AU - Buie, Stephanie

AU - Diehl, Anna Mae

AU - Guy, Cynthia

AU - Kigongo, Christopher

AU - Pan, Yi Ping

AU - Chalasani, Naga

AU - Cummings, Oscar

AU - Ghabril, Marwan

AU - Molleston, Jean

AU - Sandrasegaran, Kumar

AU - Subbarao, Girish

AU - Vuppalanchi, Raj

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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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U2 - 10.1111/apt.13824

DO - 10.1111/apt.13824

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