Influence of Adiponutrin in Chronic Liver Disease

Alcoholic Liver Disease Clinical Trial

Official title:

Study of Metabolism Influence in Human Alcoholic Liver Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01122797
• Other study ID #: ET-PNPLA3
• Status: Completed
• Phase: N/A
• First received: May 11, 2010
• Last updated: May 11, 2010
• Start date: January 2003
• Est. completion date: March 2010

Study information

• Verified date: December 2002
• Source: Erasme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 658
• Est. completion date: March 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Alcoholic Liver Disease
• Liver Diseases
• Liver Diseases, Alcoholic

Locations

Country	Name	City	State
Belgium	Hopital Erasme- Dpt of Gastroenterology	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Erasme University Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (8)

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. doi: 10.1074/jbc.M109.064501. Epub 2009 Dec 23. — View Citation

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. doi: 10.1073/pnas.1003585107. Epub 2010 Apr 12. — View Citation

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. doi: 10.1007/s00125-009-1285-z. Epub 2009 Feb 18. — View Citation

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. doi: 10.1053/j.gastro.2009.06.005. Epub 2009 Jun 12. — View Citation

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. doi: 10.1038/ng.257. Epub 2008 Sep 25. — View Citation

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. doi: 10.1038/ng.488. Epub 2009 Nov 29. — View Citation

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. doi: 10.1002/hep.23622. — View Citation

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. doi: 10.1016/j.ajhg.2008.09.012. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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