Influence of Adiponutrin in Chronic Liver Disease - Full Text View

Purpose

Increasing evidence attests the influence of multiple metabolic genetic risk factors in the progression of alcoholic liver disease. Deleterious pathways involved in metabolism such as lipid peroxidation and cytokines have been implicated in promoting inflammation leading to fibrosis increase and liver injury progression. The aim of this study was to assess the role of rs738409 single nucleotide polymorphism in the PNPLA3 gene in alcoholic liver disease patients.

Condition
Alcoholic Liver Disease

Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Cross-Sectional
Official Title:	Study of Metabolism Influence in Human Alcoholic Liver Disease

Resource links provided by NLM:

MedlinePlus related topics: Liver Diseases

U.S. FDA Resources

Further study details as provided by Erasme University Hospital:

Primary Outcome Measures:

Assessment of fibrosis and steatosis by liver biopsy in alcoholic liver disease patients.
After liver histology assessment for liver liver dammage a potential correlation of fibrosis and steatosis was studied with rs738409 PNPLA3 polymorphism

Biospecimen Retention: Samples With DNA

DNA extraction from whole blood sample. Piece of liver tissue in the alcoholic liver disease group.

Enrollment:	658
Study Start Date:	January 2003
Study Completion Date:	March 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts
Alcoholic liver disease Alcoholic liver disease patients undergoing a transjugular liver biopsy in our institution
Controls Healthy controls patients recruited from the Occupational Medicine Department during a routine physical examination.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Probability Sample

Study Population

Consecutive patients undergoing transjugular liver biopsy for alcoholic liver disease will be included in the study to determine the potential correlation between rs738409 PNPLA3 polymorphism and/or PNPLA3 mRNA expression.

Criteria

ALD patients:

Inclusion Criteria:

Excess alcohol intake
Abnormal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) or a suspicion of cirrhosis related to ALD
Caucasian ethnicity

Exclusion Criteria:

Presence of any other chronic liver disease
Co-infection with human immunodeficiency virus

Controls:

Inclusion Criteria:

Caucasian ethnicity

Exclusion Criteria:

Presence of a disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01122797

Locations

Belgium
Hopital Erasme- Dpt of Gastroenterology
Brussels, Belgium, 1070

Sponsors and Collaborators

Erasme University Hospital

More Information

Publications:

Tian C, Stokowski RP, Kershenobich D, Ballinger DG, Hinds DA. Variant in PNPLA3 is associated with alcoholic liver disease. Nat Genet. 2010 Jan;42(1):21-3. Epub 2009 Nov 29.

Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008 Dec;40(12):1461-5. Epub 2008 Sep 25.

Yuan X, Waterworth D, Perry JR, Lim N, Song K, Chambers JC, Zhang W, Vollenweider P, Stirnadel H, Johnson T, Bergmann S, Beckmann ND, Li Y, Ferrucci L, Melzer D, Hernandez D, Singleton A, Scott J, Elliott P, Waeber G, Cardon L, Frayling TM, Kooner JS, Mooser V. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet. 2008 Oct;83(4):520-8.

Huang Y, He S, Li JZ, Seo YK, Osborne TF, Cohen JC, Hobbs HH. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7892-7. Epub 2010 Apr 12.

He S, McPhaul C, Li JZ, Garuti R, Kinch L, Grishin NV, Cohen JC, Hobbs HH. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem. 2010 Feb 26;285(9):6706-15. Epub 2009 Dec 23.

Kotronen A, Peltonen M, Hakkarainen A, Sevastianova K, Bergholm R, Johansson LM, Lundbom N, Rissanen A, Ridderstråle M, Groop L, Orho-Melander M, Yki-Järvinen H. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 2009 Sep;137(3):865-72. Epub 2009 Jun 12.

Kotronen A, Johansson LE, Johansson LM, Roos C, Westerbacka J, Hamsten A, Bergholm R, Arkkila P, Arola J, Kiviluoto T, Fisher RM, Ehrenborg E, Orho-Melander M, Ridderstråle M, Groop L, Yki-Järvinen H. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia. 2009 Jun;52(6):1056-60. Epub 2009 Feb 18.

Valenti L, Al-Serri A, Daly AK, Galmozzi E, Rametta R, Dongiovanni P, Nobili V, Mozzi E, Roviaro G, Vanni E, Bugianesi E, Maggioni M, Fracanzani AL, Fargion S, Day CP. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2010 Apr;51(4):1209-17.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Trépo E, Gustot T, Degré D, Lemmers A, Verset L, Demetter P, Ouziel R, Quertinmont E, Vercruysse V, Amininejad L, Deltenre P, Le Moine O, Devière J, Franchimont D, Moreno C. Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease. J Hepatol. 2011 Oct;55(4):906-12. Epub 2011 Feb 18.

Responsible Party:	Eric Trépo, MD, Erasme University Hospital (Olivier Le Moine, MD, PhD)
ClinicalTrials.gov Identifier:	NCT01122797 History of Changes
Other Study ID Numbers:	ET-PNPLA3
Study First Received:	May 11, 2010
Last Updated:	May 11, 2010
Health Authority:	Belgium: Institutional Review Board

Keywords provided by Erasme University Hospital:

PNPLA3
fibrosis
cirrhosis
alcoholic liver disease

Additional relevant MeSH terms:

Liver Diseases
Liver Diseases, Alcoholic
Digestive System Diseases

Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders

ClinicalTrials.gov processed this record on May 23, 2013