title: Studies of the association of the GNB3 825C>T polymorphism with components of the metabolic syndrome in white Danes.
abstract: OBJECTIVE
  The 825C>T polymorphism in the gene encoding the G protein beta3 subunit (GNB3) causes enhanced G protein activation and increased in vitro cell proliferation. This polymorphism is also repeatedly associated with an increased risk of hypertension and has been studied in relation to obesity with divergent results. Only a few association studies have investigated whether this polymorphism is related to type 2 diabetes or the metabolic syndrome. We estimated the impact of the GNB3 825C>T polymorphism in relatively large-scale association studies of common phenotypes of the metabolic syndrome.
  
  
  METHODS
  The GNB3 825C>T polymorphism was genotyped in 7,518 white Danish subjects using mass spectrometry analysis of PCR products. Case-control studies were undertaken for obesity, hypertension, type 2 diabetes and the metabolic syndrome, and a meta-analysis including data from the present study and previous studies of hypertension was performed. Quantitative trait studies of metabolic variables were carried out in 4,387 glucose-tolerant subjects.
  
  
  RESULTS
  We observed minor differences in 825C>T genotype distributions for type 2 diabetes (CC/CT/TT 49/41/10% (control) vs 46/46/9% (cases), respectively, p=0.007); however, after correction for multiple testing, these were not statistically significant. No association was found with hypertension, obesity or the metabolic syndrome. Curiously, the T allele was associated with nominally lower systolic and diastolic blood pressure levels-a finding in contrast with most previous studies-but not with other metabolic variables. Meta-analysis demonstrated a high degree of heterogeneity between study populations of different ethnic origin. Although there was a tendency towards an increased risk of hypertension among 825T allele carriers, this was not statistically significant.
  
  
  CONCLUSIONS
  The present study suggests no major involvement of the GNB3 825C>T polymorphism in components of the metabolic syndrome.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 2, NSH2.16, 2820 Gentofte, Denmark. gtta@steno.dk
authors.forename: G
authors.initials: G
authors.lastname: Andersen
authors.forename: J
authors.initials: J
authors.lastname: Overgaard
authors.forename: A
authors.initials: A
authors.lastname: Albrechtsen
authors.forename: C
authors.initials: C
authors.lastname: Glümer
authors.forename: K
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: T
authors.initials: T
authors.lastname: Jørgensen
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003718:Denmark; D005215:Fasting; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D001786:Blood Glucose; C454420:G-protein beta3 subunit; D020962:Heterotrimeric GTP-Binding Proteins