Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease

Background & Aims Chronic liver disease presents a major global public health challenge. Stratification of asymptomatic, at-risk patients in primary care using non-invasive methods has the potential to address this by identifying those likely to progress. We therefore evaluated variant alleles...

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Main Authors: Grove, Jane I., Thiagarajan, Prarthana, Astbury, Stuart, Harris, Rebecca, Delahooke, Toby, Guha, Indra Neil, Aithal, Guruprasad P.
Format: Article
Language:English
Published: Wiley 2018
Subjects:
Online Access:https://eprints.nottingham.ac.uk/50349/
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author Grove, Jane I.
Thiagarajan, Prarthana
Astbury, Stuart
Harris, Rebecca
Delahooke, Toby
Guha, Indra Neil
Aithal, Guruprasad P.
author_facet Grove, Jane I.
Thiagarajan, Prarthana
Astbury, Stuart
Harris, Rebecca
Delahooke, Toby
Guha, Indra Neil
Aithal, Guruprasad P.
author_sort Grove, Jane I.
building Nottingham Research Data Repository
collection Online Access
description Background & Aims Chronic liver disease presents a major global public health challenge. Stratification of asymptomatic, at-risk patients in primary care using non-invasive methods has the potential to address this by identifying those likely to progress. We therefore evaluated variant alleles at loci associated with non-alcoholic fatty liver disease (NAFLD) as genetic determinants of substantial liver injury in patients with disease risk factors. Methods Levels of serum procollagen III (PIIINP), an established fibrosis and steatohepatitis marker, were determined in 467 people who had type 2 diabetes and/or BMI>27.3 (identified from registration with general practitioners) in this observational cross-sectional study. Patients were genotyped for characterised risk alleles in PNPLA3 (rs738409), GCKR (rs1260326) and TM6SF2 (rs58542926) and associations with PIIINP assessed. Results The risk alleles in PNPLA3, GCKR or TM6SF2 were not found to be individually associated with the presence of a disease risk factor and were not significantly more common in patients with raised serum PIIINP. The prevalence of possession of both PNPLA3 and GCKR variant alleles combined was significantly higher in at-risk patients with clinically significant liver disease indicated by serum PIIINP above 11 ng/ml (P=0.014). Conclusions Genotyping therefore has limited value for predicting severe liver disease in at-risk individuals identified in a community setting.
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spelling nottingham-503492019-03-15T04:30:19Z https://eprints.nottingham.ac.uk/50349/ Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease Grove, Jane I. Thiagarajan, Prarthana Astbury, Stuart Harris, Rebecca Delahooke, Toby Guha, Indra Neil Aithal, Guruprasad P. Background & Aims Chronic liver disease presents a major global public health challenge. Stratification of asymptomatic, at-risk patients in primary care using non-invasive methods has the potential to address this by identifying those likely to progress. We therefore evaluated variant alleles at loci associated with non-alcoholic fatty liver disease (NAFLD) as genetic determinants of substantial liver injury in patients with disease risk factors. Methods Levels of serum procollagen III (PIIINP), an established fibrosis and steatohepatitis marker, were determined in 467 people who had type 2 diabetes and/or BMI>27.3 (identified from registration with general practitioners) in this observational cross-sectional study. Patients were genotyped for characterised risk alleles in PNPLA3 (rs738409), GCKR (rs1260326) and TM6SF2 (rs58542926) and associations with PIIINP assessed. Results The risk alleles in PNPLA3, GCKR or TM6SF2 were not found to be individually associated with the presence of a disease risk factor and were not significantly more common in patients with raised serum PIIINP. The prevalence of possession of both PNPLA3 and GCKR variant alleles combined was significantly higher in at-risk patients with clinically significant liver disease indicated by serum PIIINP above 11 ng/ml (P=0.014). Conclusions Genotyping therefore has limited value for predicting severe liver disease in at-risk individuals identified in a community setting. Wiley 2018-03-01 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/50349/1/FINAL%20upload%20liv%20int%20geno%20manuscript%20220218.pdf Grove, Jane I., Thiagarajan, Prarthana, Astbury, Stuart, Harris, Rebecca, Delahooke, Toby, Guha, Indra Neil and Aithal, Guruprasad P. (2018) Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease. Liver International . ISSN 1478-3231 PNPLA3 GCKR TM6SF2 NAFLD http://onlinelibrary.wiley.com/doi/10.1111/liv.13733/abstract doi:10.1111/liv.13733 doi:10.1111/liv.13733
spellingShingle PNPLA3
GCKR
TM6SF2
NAFLD
Grove, Jane I.
Thiagarajan, Prarthana
Astbury, Stuart
Harris, Rebecca
Delahooke, Toby
Guha, Indra Neil
Aithal, Guruprasad P.
Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease
title Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease
title_full Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease
title_fullStr Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease
title_full_unstemmed Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease
title_short Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease
title_sort analysis of genotyping for predicting liver injury marker, procollagen iii in persons at risk of non-alcoholic fatty liver disease
topic PNPLA3
GCKR
TM6SF2
NAFLD
url https://eprints.nottingham.ac.uk/50349/
https://eprints.nottingham.ac.uk/50349/
https://eprints.nottingham.ac.uk/50349/