NCT01122797

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
658

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Jan 2003

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2003

Completed
7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2010

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2010

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

May 11, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 13, 2010

Completed
Last Updated

May 13, 2010

Status Verified

December 1, 2002

Enrollment Period

7 years

First QC Date

May 11, 2010

Last Update Submit

May 11, 2010

Conditions

Alcoholic Liver Disease

Keywords

PNPLA3fibrosiscirrhosisalcoholic liver disease

Outcome Measures

Primary Outcomes (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

Study Arms (2)

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 Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability 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.

You may qualify if:

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

You may not qualify if:

  • Presence of any other chronic liver disease
  • Co-infection with human immunodeficiency virus
  • Controls:
  • Caucasian ethnicity
  • Presence of a disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hopital Erasme- Dpt of Gastroenterology

Brussels, 1070, Belgium

Location

Related Publications (9)

  • 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.

    PMID: 19946271BACKGROUND

  • 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.

    PMID: 18820647BACKGROUND

  • 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.

    PMID: 18940312BACKGROUND

  • 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.

    PMID: 20385813BACKGROUND

  • 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.

    PMID: 20034933BACKGROUND

  • Kotronen A, Peltonen M, Hakkarainen A, Sevastianova K, Bergholm R, Johansson LM, Lundbom N, Rissanen A, Ridderstrale M, Groop L, Orho-Melander M, Yki-Jarvinen 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.

    PMID: 19524579BACKGROUND

  • 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, Ridderstrale M, Groop L, Yki-Jarvinen 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.

    PMID: 19224197BACKGROUND

  • 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.

    PMID: 20373368BACKGROUND

  • Trepo E, Gustot T, Degre D, Lemmers A, Verset L, Demetter P, Ouziel R, Quertinmont E, Vercruysse V, Amininejad L, Deltenre P, Le Moine O, Deviere 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. doi: 10.1016/j.jhep.2011.01.028. Epub 2011 Feb 18.

    PMID: 21334404DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Conditions

Liver Diseases, AlcoholicFibrosis

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesAlcohol-Induced DisordersAlcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER

Study Record Dates

First Submitted

May 11, 2010

First Posted

May 13, 2010

Study Start

January 1, 2003

Primary Completion

January 1, 2010

Study Completion

March 1, 2010

Last Updated

May 13, 2010

Record last verified: 2002-12

Locations

BE(1)