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 ≥30 kg/m2. 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.
Address correspondence and reprint requests to Dr. Thomas J. Hudson or Dr. James C. Engert, Montreal Genome Centre, MGHRI/MUHC, Montréal, Québec, Canada H3G 1A4. E-mail:or .
Received for publication 12 November 2001 and accepted in revised form 22 January 2002.
D.A. is a member of the Clinical Genomics Advisory Board at Merck Research Labs, a company that markets drugs used to treat diabetes. He is also a member of the Scientific Advisory Board of Genomics Collaborative, a company that performs diabetes research. Neither company was involved in the research described in this study. T.J.H. has received grant/research support from Bristol-Myers Squibb, Millennium Pharmaceuticals, and Affymetrix. Part of this grant support was used to fund this research.
*J.C.E., M.-C.V., and S.M.W. contributed equally to this study.
J.C.E., M.-C.V., and S.M.W. contributed equally to this study.
IGT, impaired glucose tolerance; LD, linkage disequilibrium; OR, odds ratio; PPAR, peroxisome proliferator-activated receptor; QC, Quebec City; QTDT, quantitative transmission disequilibrium test; SLSJ, Saguenay-Lac-St-Jean; SNP, single-nucleotide polymorphism; TZD, thiazolidinedione.