title: Mutation screen and association studies in the diacylglycerol O-acyltransferase homolog 2 gene (DGAT2), a positional candidate gene for early onset obesity on chromosome 11q13.
abstract: BACKGROUND
  DGAT2 is a promising candidate gene for obesity because of its function as a key enzyme in fat metabolism and because of its localization on chromosome 11q13, a linkage region for extreme early onset obesity detected in our sample. We performed a mutation screen in 93 extremely obese children and adolescents and 94 healthy underweight controls. Association studies were performed in samples of up to 361 extremely obese children and adolescents and 445 healthy underweight and normal weight controls. Additionally, we tested for linkage and performed family based association studies at four common variants in the 165 families of our initial genome scan.
  
  
  RESULTS
  The mutation screen revealed 15 DNA variants, four of which were coding non-synonymous exchanges: p.Val82Ala, p.Arg297Gln, p.Gly318Ser and p.Leu385Val. Ten variants were synonymous: c.-9447A > G, c.-584C > G, c.-140C > T, c.-30C > T, IVS2-3C > G, c.812A > G, c.920T > C, IVS7+23C > T, IVS7+73C > T and *22C > T. Additionally, the small biallelic trinucleotide repeat rs3841596 was identified. None of the case control and family based association studies showed an association of investigated variants or haplotypes in the genomic region of DGAT2.
  
  
  CONCLUSIONS
  In conclusion, our results do not support the hypothesis of an important role of common genetic variation in DGAT2 for the development of obesity in our sample. Anyhow, if there is an influence of genetic variation in DGAT2 on body weight regulation, it might either be conferred by the less common variants (MAF < 0.1) or the detected, rare non-synonymous variants.
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany. Susann.Friedel@uni-due.de <Susann.Friedel@uni-due.de>
authors.forename: Susann
authors.initials: S
authors.lastname: Friedel
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reichwald
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.forename: Harald
authors.initials: H
authors.lastname: Brumm
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Wermter
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Fries
authors.forename: Kerstin
authors.initials: K
authors.lastname: Koberwitz
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.forename: Heike
authors.initials: H
authors.lastname: Biebermann
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002648:Child; D002880:Chromosomes, Human, Pair 11; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers; C494885:DGAT2 protein, human; D051048:Diacylglycerol O-Acyltransferase