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: 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 ] [ Designated as safety issue: No ]gene mutation allele variation identification measure via gene extraction
- hepatic fat content [ Time Frame: 2 years ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (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
To establish a cohort of obese youths to prospectively analyze potential factors (genetic and nutritional factors) that might affect the expression and progression of NAFLD. This study will determine genetic markers and their ability to convey susceptibility to NAFLD in obese children and adolescents. Furthermore, potential mechanisms that might contribute to the accumulation of hepatic Triglyceride (TG) accumulation will be, for the first time, assessed by genotyping. Additionally, we will examine the presence of intestinal microbiome in the development of fatty liver through stool collection.
|Contact: Melissa Shaw, B.A.||email@example.com|
|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|