Influence of Adiponutrin in Chronic Liver Disease

• Sponsor: Erasme University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01122797
• Collaborator: (none)
• Enrollment: 658
• Location: 1
• Duration (Months): 85.9
• Patients Per Site Per Month: 7.7

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Alcoholic Liver Disease

Study Design

• Study Type: Observational
• Actual Enrollment: 658 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Study of Metabolism Influence in Human Alcoholic Liver Disease
• Study Start Date: Jan 1, 2003
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Hopital Erasme- Dpt of Gastroenterology	Brussels		Belgium	1070

Sponsors and Collaborators

• Erasme University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• ClinicalTrials.gov Identifier: NCT01122797
• Other Study ID Numbers: ET-PNPLA3
• First Posted: May 13, 2010
• Last Update Posted: May 13, 2010
• Last Verified: Dec 1, 2002

• Keywords provided by , ,: PNPLA3; fibrosis; cirrhosis; alcoholic liver disease
• Additional relevant MeSH terms: Liver Diseases; Liver Diseases, Alcoholic

Study Results

No Results Posted as of May 13, 2010