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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.

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


Authors

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JANE GROVE jane.grove@nottingham.ac.uk
Assistant Professor

Prarthana Thiagarajan

Rebecca Harris

Toby Delahooke

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NEIL GUHA neil.guha@nottingham.ac.uk
Professor of Hepatology



Abstract

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.

Citation

Grove, J. I., Thiagarajan, P., Astbury, S., Harris, R., Delahooke, T., Guha, I. N., & Aithal, G. P. (2018). Analysis of genotyping for predicting liver injury marker, Procollagen III in persons at risk of non-alcoholic fatty liver disease. Liver International, 38(10), 1832-1838. https://doi.org/10.1111/liv.13733

Journal Article Type Article
Acceptance Date Feb 21, 2018
Online Publication Date Mar 1, 2018
Publication Date 2018-10
Deposit Date Mar 9, 2018
Publicly Available Date Mar 29, 2024
Journal Liver International
Print ISSN 1478-3223
Electronic ISSN 1478-3231
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 38
Issue 10
Pages 1832-1838
DOI https://doi.org/10.1111/liv.13733
Keywords PNPLA3, GCKR, TM6SF2, NAFLD
Public URL https://nottingham-repository.worktribe.com/output/918179
Publisher URL http://onlinelibrary.wiley.com/doi/10.1111/liv.13733/abstract

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