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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
NR1H4 rs35724 G>C variant modulates liver damage in nonalcoholic fatty liver disease
Liver International, Volume 41, No. 11, Year 2021
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Description
Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G>C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms were genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n = 124). Results: The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic confounders and for enrolling centre, was protective against severity of steatosis (GG vs CC OR 0.77, 95% CI 0.62-0.95; P =.01), steatohepatitis (GG vs CC OR 0.62, 95% CI 0.47-0.83; P =.001) and severity of fibrosis (GG vs CC OR 0.83, 95% CI 0.67-0.98; P =.04). The C allele was associated with higher total circulating cholesterol (P =.01). Patients carrying the NR1H4 rs35724 C allele had significantly higher hepatic mRNA levels of FXR and were associated with higher hepatic FGFR4 and Cyp39A1 that are in turn involved in bile acid synthesis. Conclusions: Increased hepatic FXR expression due to the NR1H4 rs35724 C allele is linked to higher serum cholesterol but protects against steatosis, steatohepatitis and liver fibrosis. The translational relevance of these results for patient risk stratification and FXR-targeted therapy warrants further investigation. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Authors & Co-Authors
Pihlajamäki, Jussi
Finland, Kuopio
Itä-suomen Yliopisto
Eslam, Mohammed
Australia, Parramatta
The Westmead Institute for Medical Research
Yki-Jar̈vinen, Hannele
Finland, Helsinki
Helsingin Yliopisto
Baselli, Guido
Italy, Milan
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
Camma, Calogero
Italy, Palermo
Università Degli Studi Di Palermo
Di Marco, Vito
Italy, Palermo
Università Degli Studi Di Palermo
Enea, Marco
Italy, Palermo
Università Degli Studi Di Palermo
Pennisi, Grazia
Italy, Palermo
Università Degli Studi Di Palermo
Prati, Daniele
Italy, Milan
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
Fracanzani, Anna Ludovica Udovica
Italy, Milan
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
Craxi, Antonio
Italy, Palermo
Università Degli Studi Di Palermo
George, Jacob A.
Australia, Parramatta
The Westmead Institute for Medical Research
Valenti, Luca Vittorio Carlo
Italy, Milan
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
Italy, Milan
Università Degli Studi Di Milano
Petta, Salvatore
Italy, Palermo
Università Degli Studi Di Palermo
Statistics
Citations: 4
Authors: 14
Affiliations: 7
Identifiers
Doi:
10.1111/liv.15016
ISSN:
14783223
Research Areas
Genetics And Genomics
Health System And Policy
Noncommunicable Diseases
Study Design
Cohort Study