TY - JOUR
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, James 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 - 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 - Piercy, Dawn
AU - Wagner, Melissa
AU - Alazraki, Adina
AU - Cleeton, Rebecca
AU - Karpen, Saul
AU - Raviele, Nicholas
AU - Vos, Miriam
AU - Byam, Elizabeth
AU - Noureddin, Mazen
N1 - Publisher Copyright:
© 2016 John Wiley & Sons Ltd
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.
UR - http://www.scopus.com/inward/record.url?scp=84995790720&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995790720&partnerID=8YFLogxK
U2 - 10.1111/apt.13824
DO - 10.1111/apt.13824
M3 - Article
C2 - 27730688
AN - SCOPUS:84995790720
SN - 0269-2813
VL - 44
SP - 1253
EP - 1264
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 11-12
ER -