title: -391 C to G substitution in the regulator of G-protein signalling-2 promoter increases susceptibility to the metabolic syndrome in white European men: consistency between molecular and epidemiological studies.
abstract: BACKGROUND
  The regulator of G-protein signalling-2 (RGS2) is a key factor in adipogenesis. We hypothesized that the metabolic syndrome, of which obesity is an important component, might be related to genetic variation in RGS2.
  
  
  RESULTS
  We screened the human RGS2 gene. We tested the functionality of a common genetic variant in vitro, ex vivo, and in epidemiological study involving six European populations. The C to G substitution at position -391 in the RGS2 promoter was associated with enhanced RGS2 expression in vitro in transfected 3T3-L1 adipocytes and Chinese hamster cells and ex vivo in adipocytes from male, but not female, volunteers. In 2732 relatives from 512 families and 348 unrelated individuals, randomly recruited from six European populations, the prevalence of GG homozygosity was 54.1%. The metabolic syndrome score, a composite of six continuous traits making up this clinical entity, was 0.27 standardized units higher (P < 0.001) in 795 GG homozygous men compared with 683 men carrying the C allele. Transmission of the -391 G allele to male offspring was associated with a 0.20 unit increase in the score (P=0.039). These epidemiological relations were not significant in 1602 women.
  
  
  CONCLUSIONS
  The C to G substitution at position -391 in the RGS2 promoter increases RGS2 expression in adipocytes and is associated with the metabolic syndrome in white European men. Further experimental and clinical research should establish whether this common polymorphism might be a target for preventive or therapeutic intervention.
authors.affiliation: Center for Molecular and Vascular Biology, University Hospital Gasthuisberg, University of Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Freson
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Stolarz
authors.forename: Raymond
authors.initials: R
authors.lastname: Aerts
authors.forename: Eva
authors.initials: E
authors.lastname: Brand
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Brand-Herrmann
authors.forename: Kalina
authors.initials: K
authors.lastname: Kawecka-Jaszcz
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kuznetsova
authors.forename: Valérie
authors.initials: V
authors.lastname: Tikhonoff
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.forename: Jos
authors.initials: J
authors.lastname: Vermylen
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
authors.forename: Chris
authors.initials: C
authors.lastname: Van Geet
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000328:Adult; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003596:Cytosine; D005060:Europe / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006147:Guanine; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012727:Sex Characteristics; D017678:Sex Distribution; D012737:Sex Factors; D014162:Transfection; D044465:White People / Q000235:genetics*
chemical_list: D020710:RGS Proteins; C087182:RGS2 protein, human; D006147:Guanine; D003596:Cytosine