Genetics of Fatty Liver Disease in Childhood Obesity.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Non Alcoholic Fatty Liver Disease
- Sponsor
- Yale University
- Enrollment
- 381
- Locations
- 1
- Primary Endpoint
- gene expression
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Sonia Caprio
Principal Investigator
Yale University
Eligibility Criteria
Inclusion Criteria
- •between 7 and 18 years of age,
- •overweight or obese with a BMI greater than the 85th percentile for age and gender, and
- •be otherwise healthy.
Exclusion Criteria
- •the use of any medication that alters liver function, blood pressure, glucose or lipid metabolism and
- •no use of any antipsychotic medication
- •Youth on chronic anti-inflammatory medications or who consume alcohol are also excluded.
Outcomes
Primary Outcomes
gene expression
Time Frame: Baseline
gene mutation allele variation identification measure via gene extraction
Secondary Outcomes
- glucose tolerance(2 years)
- hepatic fat content(2 years)