5' flanking variants of resistin are associated with obesity.
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.
Engert
James C
JC
Montreal Genome Centre, McGill University Health Centre Research Institute, Montréal, Canada.
Vohl
Marie-Claude
MC
Williams
Scott M
SM
Lepage
Pierre
P
Loredo-Osti
J C
JC
Faith
Janet
J
Doré
Carole
C
Renaud
Yannick
Y
Burtt
Noël P
NP
Villeneuve
Amélie
A
Hirschhorn
Joel N
JN
Altshuler
David
D
Groop
Leif C
LC
Després
Jean-Pierre
JP
Gaudet
Daniel
D
Hudson
Thomas J
TJ
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
D020121:5' Untranslated Regions; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D052243:Resistin