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Genetic Variants Associated With Obesity and Insulin Resistance in Hispanic Boys With Nonalcoholic Fatty Liver Disease
- Source :
- Journal of pediatric gastroenterology and nutrition. 66(5)
- Publication Year :
- 2018
-
Abstract
- BACKGROUND AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic boys. Further, obesity and insulin resistance are major risk factors for NAFLD. No gene localization studies had been performed on children with biopsy-proven NAFLD. This study aims to identify genomic variants associated with increased adiposity and insulin resistance in a population of children with varying histologic severity of NAFLD. METHODS: We conducted a genome-wide association scan (GWAS) including 624,297 single nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in 234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research Network Studies. Traits were examined quantitatively using linear regression. SNPs with p-value 5% were considered potentially significant. RESULTS: Evaluated subjects had a median age of 12.0 years, BMI of 31.4, and hemoglobin A1C (Hgb A1C) of 5.3. The prevalence of NAFL, borderline NASH and definite NASH were 23%, 53%, and 22%, respectively. The GWAS identified 10 SNPs that were associated with BMI z-score, 6 within chromosome 2, and 1 within CAMK1D, which has a potential role in liver gluconeogenesis. In addition, the GWAS identified 9 novel variants associated with insulin resistance: HOMA-IR (6) and HbA1c (3). CONCLUSIONS: This study of Hispanic boys with biopsy-proven NAFLD with increased risk for the metabolic syndrome revealed novel genetic variants that are associated with obesity and insulin resistance.
- Subjects :
- 0301 basic medicine
Blood Glucose
Male
Pediatric Obesity
Genotyping Techniques
Genome-wide association study
030204 cardiovascular system & hematology
Gastroenterology
Body Mass Index
Cohort Studies
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Risk Factors
Nonalcoholic fatty liver disease
Prevalence
Insulin
Longitudinal Studies
Prospective Studies
Prospective cohort study
Child
Adiposity
Hispanic or Latino
Lipids
Liver
Cohort study
medicine.medical_specialty
Adolescent
digestive system
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
Insulin resistance
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Glycated Hemoglobin
business.industry
nutritional and metabolic diseases
Genetic Variation
medicine.disease
Obesity
digestive system diseases
030104 developmental biology
Pediatrics, Perinatology and Child Health
Steatohepatitis
Insulin Resistance
business
Body mass index
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15364801
- Volume :
- 66
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of pediatric gastroenterology and nutrition
- Accession number :
- edsair.doi.dedup.....6cf13c117173db69d919fa1e08485f79