title: 5' flanking variants of resistin are associated with obesity.
abstract: Diabetes and obesity have long been known to be related. The recently characterized adipocyte hormone resistin (also called FIZZ3/ADSF) has been implicated as a molecular link between impaired glucose tolerance (IGT) and obesity in mice. A search for sequence variants at the human resistin locus identified nine single-nucleotide polymorphisms (SNPs) but no coding variants. An investigation into the association of these SNPs with diabetes and obesity revealed two 5' flanking variants (g.-537 and g.-420), in strong linkage disequilibrium, that are associated with BMI. In nondiabetic individuals from the Quebec City area and the Saguenay-Lac-St-Jean region of Quebec, the g.-537 mutation (allelic frequency = 0.04) was significantly associated with an increase in BMI (P = 0.03 and P = 0.01, respectively). When the data from these two populations were combined and adjusted for age and sex, both the g.-537 (odds ratio [OR] 2.72, 95% CI 1.28-5.81) and the g.-420 variants (1.58, 1.06-2.35) were associated with an increased risk for a BMI > or =30 kg/m(2). In contrast, in case/control and family-based study populations from Scandinavia, we saw no effect on BMI with either of these promoter variants. No association was seen with diabetes in any of the population samples.
authors.affiliation: Montreal Genome Centre, McGill University Health Centre Research Institute, Montréal, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.forename: Pierre
authors.initials: P
authors.lastname: Lepage
authors.forename: J C
authors.initials: JC
authors.lastname: Loredo-Osti
authors.forename: Janet
authors.initials: J
authors.lastname: Faith
authors.forename: Carole
authors.initials: C
authors.lastname: Doré
authors.forename: Yannick
authors.initials: Y
authors.lastname: Renaud
authors.forename: Noël P
authors.initials: NP
authors.lastname: Burtt
authors.forename: Amélie
authors.initials: A
authors.lastname: Villeneuve
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
authors.forename: Leif C
authors.initials: LC
authors.lastname: Groop
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D005838:Genotype; D006729:Hormones, Ectopic / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D052243:Resistin
chemical_list: D020121:5' Untranslated Regions; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D052243:Resistin