title: Genetic variants near the MGAT1 gene are associated with body weight, BMI and fatty acid metabolism among adults and children.
abstract: OBJECTIVE
  Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-β-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men.
  
  
  METHODS
  Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children.
  
  
  RESULTS
  Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95% confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95% CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95% CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95% CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95%CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95% CI:0.093-0.373, P=0.001) and 0.147 (95% CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038).
  
  
  CONCLUSIONS
  Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity.
authors.affiliation: Department of Neuroscience, Functional pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: J A
authors.initials: JA
authors.lastname: Jacobsson
authors.forename: M
authors.initials: M
authors.lastname: Rask-Andersen
authors.forename: U
authors.initials: U
authors.lastname: Risérus
authors.forename: G
authors.initials: G
authors.lastname: Moschonis
authors.forename: A
authors.initials: A
authors.lastname: Koumpitski
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: L
authors.initials: L
authors.lastname: Lannfelt
authors.forename: C
authors.initials: C
authors.lastname: Marcus
authors.forename: U
authors.initials: U
authors.lastname: Gyllensten
authors.forename: H B
authors.initials: HB
authors.lastname: Schiöth
authors.forename: R
authors.initials: R
authors.lastname: Fredriksson
mesh_terms: D000293:Adolescent; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D013548:Sweden / Q000453:epidemiology
chemical_list: D005227:Fatty Acids; C561128:MGAT1 protein, human; D017351:N-Acetylglucosaminyltransferases