Your browser doesn't support javascript.
loading
Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.
Nelson, J E; Handa, P; Aouizerat, B; Wilson, L; Vemulakonda, L A; Yeh, M M; Kowdley, K V.
  • Nelson JE; Benaroya Research Institute at Virginia Mason Medical Center, Seattle, WA, USA.
  • Handa P; Liver Care Network and Organ Care Research Program, Swedish Medical Center, Seattle, WA, USA.
  • Aouizerat B; Department of Physiological Nursing, University of California at San Francisco, San Francisco, CA, USA.
  • Wilson L; Institute for Human Genetics, University of California at San Francisco, San Francisco, CA, USA.
  • Vemulakonda LA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Yeh MM; Liver Care Network and Organ Care Research Program, Swedish Medical Center, Seattle, WA, USA.
  • Kowdley KV; Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Aliment Pharmacol Ther ; 44(11-12): 1253-1264, 2016 12.
Article en En | MEDLINE | ID: mdl-27730688
ABSTRACT

BACKGROUND:

Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1ß 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-1ß and IL-6 suppression.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Interleucina-6 / Interleucina-1beta / Enfermedad del Hígado Graso no Alcohólico Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Año: 2016 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Interleucina-6 / Interleucina-1beta / Enfermedad del Hígado Graso no Alcohólico Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Año: 2016 Tipo del documento: Article