NASH meal response study: The Study of Genetic Factors Involved in Post-Prandial Fat Processing and their contribution to the Progression of Non-Alcoholic Fatty Liver Disease

1st July 2016 - ongoing

Status: Active

Specialism: Liver, Non-Alcoholic Fatty Liver Disease (NAFLD).

Team: Professor Guruprasad AithalDr Jane Grove.

Currently, 9 members of a single family have been recruited to our NASH genotyping study (REC Ref: GM010201) presenting with symptoms of NAFLD (from simple fatty liver to cirrhosis and hepatocellular carcinoma). Other members of the family have also shown an interest in taking part in this study; this is a large family of at least 50 people spanning 4 generations.

As part of their normal clinical care, several of these patients were referred to the clinical genetics department of their local hospital (University Hospitals of Leicester NHS Trust), where detailed pedigree analysis and exon sequencing found that this high prevalence of liver disease is likely to be the consequence of a novel missense variant (mutation) in the MTTP gene. This gene encodes a key protein involved in lipid metabolism predicted to contribute to the development of NAFLD (Di Filippo, et al. 2014) and other mutations in this gene have been shown to lead to the development of abetalipoproteinemia (Wetterau, et al. 1992). Further family members have since been screened in a genetic-hepatology advisory clinic jointly by Julian Barwell and Guruprasad Aithal.

Abetalipoproteinemia is a rare inherited disorder that affects the normal absorption of dietary fats, cholesterol, and fat-soluble vitamins. The disorder is generally symptomatic at an early age and diagnosed in new-borns; the identification of this novel mutation leading to NASH in adults, provides a unique opportunity to investigate the role that a mild defect in this gene product has, in the disease mechanism and the contribution lipid metabolic pathways make to disease progression. Phenotyping studies are clinically important because the particular family members and those carrying the variant alleles do not have obvious manifestations of abetalipoproteinemia; yet have NASH progressing to cirrhosis and hepatocellular carcinoma. So, phenotyping will allow us to provide specific dietary advice and interventions, hence, better manage the individual members and family as a whole. Scientifically, phenotyping will clarify critical components of genetic variation which are leading to liver pathology in the absence of systemic manifestations of abetalipoproteinemia.

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guruprasad-aithal Professor Guruprasad Aithal Biography Professor Guruprasad P. Aithal graduated with MBBS from Kasturba Medical College, Manipal, MD (Internal Medicine) from Bangalore Medical College, Bengaluru, India and completed his specialist training in Gastroenterology in the Northern…
dr-jane-grove Dr Jane Grove I am an Assistant Professor in the Hepatology Group in the NIHR Nottingham Biomedical Research Centre and the MRC-funded Nottingham Molecular Pathology Node ( My research includes translational research projects in the following…
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