title: Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.
abstract: 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).
  
  
  
  To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Benaroya Research Institute at Virginia Mason Medical Center, Seattle, WA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Nelson
authors.affiliation: Liver Care Network and Organ Care Research Program, Swedish Medical Center, Seattle, WA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Handa
authors.affiliation: Department of Physiological Nursing, University of California at San Francisco, San Francisco, CA, USA.|Institute for Human Genetics, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Aouizerat
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wilson
authors.affiliation: Liver Care Network and Organ Care Research Program, Swedish Medical Center, Seattle, WA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Vemulakonda
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: Benaroya Research Institute at Virginia Mason Medical Center, Seattle, WA, USA.|Liver Care Network and Organ Care Research Program, Swedish Medical Center, Seattle, WA, USA.
authors.forename: K V
authors.initials: KV
authors.lastname: Kowdley
mesh_terms: D000328:Adult; D000483:Alleles; D001706:Biopsy; D005260:Female; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6