Genetics of Fatty Liver Disease in Children
This is a study to investigate genetic predisposition to hepatic steatosis and the expression of gluconeogenic and lipogenic genes in livers of obese children and adolescents.
Hypothesis 1: Common variants recently associated with variation in plasma TG levels identified in Genome Wide Association Studies (GWAS) (such as GCKR, PNPLA3) can affect accumulation of fat and subsequent development of Non Alcoholic Fatty Liver Disease (NAFLD). Gene variants act in additive or synergistic manner with progressive liver fat accumulation per additional risk allele.
Hypothesis 2: With increase in hepatic fat content NASH and fibrosis will increase. Furthermore, expression of lipogenic markers (SREBP1c) will increase.
|Non Alcoholic Fatty Liver Disease||Other: ogtt Other: genotyping Other: abdominal and liver magnetic resonance imaging Other: stool sample Other: liver biopsy|
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Genetics of Fatty Liver Disease in Childhood Obesity.|
- gene expression [ Time Frame: Baseline ]gene mutation allele variation identification measure via gene extraction
- hepatic fat content [ Time Frame: 2 years ]Abdominal MRI to measure liver fat and subcutaneous and visceral fat ratio done at baseline and 2 year follow up
- glucose tolerance [ Time Frame: 2 years ]glucose tolerance status measured by 3 hour oral glucose tolerance test done at baseline and 2 year follow up
- DNA gene sequencing of intestinal bacteria's [ Time Frame: 2 years ]Measure microbiota diversity via stool samples to understand variance of triglycerides accumulation in liver
- Use liver biopsy specimen to assess differences in gene expression, as well as inflammation. [ Time Frame: As indicated by Pediatric Hepatolgist ]liver biopsy tissue obtained when subject is scheduled for pre-ordered biopsy by hepatologist
Biospecimen Retention: Samples With DNA
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||December 2020|
|Estimated Primary Completion Date:||December 2020 (Final data collection date for primary outcome measure)|
Pediatric NAFLD Cohort
Overweight and obese children and adolescents at risk for non alcoholic fatty liver disease will undergo oral glucose tolerance testing (ogtt), genotyping, abdominal and liver magnetic resonance imaging (mri), and will provide a stool sample at baseline and at 2 year follow up. A small subset will undergo liver biopsy to test for hepatic steatosis and nonalcoholic steatohepatitis.
oral glucose tolerance testOther: genotyping
genotyping to look for risk allelesOther: abdominal and liver magnetic resonance imaging
magnetic resonance imaging scan of abdomen and liver - abdominal and liver mriOther: stool sample
stool sample taken to investigate metabolitesOther: liver biopsy
liver biopsy to examine for cellular change and steatosis
Please refer to this study by its ClinicalTrials.gov identifier: NCT01966627
|Contact: Bridget Pierpont, MAfirstname.lastname@example.org|
|United States, Connecticut|
|New Haven, Connecticut, United States, 06510|
|Contact: Bridget Pierpont, M.A. 203-785-2942|
|Principal Investigator: Sonia Caprio, M.D.|
|Principal Investigator:||Sonia Caprio, M.D.||Yale University|