title: Hepatocyte nuclear factor 4 alpha polymorphisms and the metabolic syndrome in French-Canadian youth.
abstract: OBJECTIVE
  Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription factor involved in the regulation of serum glucose and lipid levels. Several HNF4A gene variants have been associated with the risk of developing type 2 diabetes mellitus. However, no study has yet explored its association with insulin resistance and the cardiometabolic risk in children. We aimed to investigate the relationship between HNF4A genetic variants and the presence of metabolic syndrome (MetS) and metabolic parameters in a pediatric population.
  
  
  METHODS
  Our study included 1,749 French-Canadians aged 9, 13 and 16 years and evaluated 24 HNF4A polymorphisms that were previously identified by sequencing.
  
  
  RESULTS
  Analyses revealed that, after correction for multiple testing, one SNP (rs736824; P<0.022) and two haplotypes (P1 promoter haplotype rs6130608-rs2425637; P<0.032 and intronic haplotype rs736824-rs745975-rs3212183; P<0.025) were associated with the risk of MetS. Additionally, a significant association was found between rs3212172 and apolipoprotein B levels (coefficient: -0.14 ± 0.05; P<0.022). These polymorphisms are located in HNF4A P1 promoter or in intronic regions.
  
  
  CONCLUSIONS
  Our study demonstrates that HNF4α genetic variants are associated with the MetS and metabolic parameters in French Canadian children and adolescents. This study, the first exploring the relation between HNF4A genetic variants and MetS and metabolic variables in a pediatric cohort, suggests that HNF4α could represent an early marker for the risk of developing type 2 diabetes mellitus.
authors: Research Institute, McGill University, Montreal, Quebec, Canada, H3G 1A4.
authors: Valérie
authors: V
authors: Marcil
authors: Department of Pediatrics, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada, H3T 1C5.
authors: Devendra
authors: D
authors: Amre
authors: Research Institute, McGill University, Montreal, Quebec, Canada, H3G 1A4; Canadian Institutes for Health Research Team on the Digestive Epithelium, Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4.
authors: Ernest G
authors: EG
authors: Seidman
authors: Canadian Institutes for Health Research Team on the Digestive Epithelium, Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4.
authors: François
authors: F
authors: Boudreau
authors: Canadian Institutes for Health Research Team on the Digestive Epithelium, Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4.
authors: Fernand P
authors: FP
authors: Gendron
authors: Canadian Institutes for Health Research Team on the Digestive Epithelium, Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4.
authors: Daniel
authors: D
authors: Ménard
authors: Canadian Institutes for Health Research Team on the Digestive Epithelium, Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4.
authors: Jean François
authors: JF
authors: Beaulieu
authors: Department of Pediatrics, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada, H3T 1C5.
authors: Daniel
authors: D
authors: Sinnett
authors: Department of Pediatrics, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada, H3T 1C5.
authors: Marie
authors: M
authors: Lambert
authors: Canadian Institutes for Health Research Team on the Digestive Epithelium, Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4; Department of Nutrition, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada, H3T 1C5.
authors: Emile
authors: E
authors: Levy
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002170:Canada / Q000453:epidemiology / Q000208:ethnology; D002648:Child; D005260:Female; D006239:Haplotypes; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D051557:Hepatocyte Nuclear Factor 4; D007328:Insulin; D008055:Lipids