This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ma, X. Articles by Doria, A. Search for Related Content PubMed PubMed Citation Articles by Ma, X. Articles by Doria, A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM UniGene Medline Plus Health Information Diabetes

Genetic Variants at the Resistin Locus and Risk of Type 2 Diabetes in Caucasians

Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center (X.M., J.H.W., A.D.), and Department of Medicine, Harvard Medical School (X.M., A.D.), Boston, Massachusetts 02215; Unit of Endocrinology, Ospedale Casa Sollievo della Sofferenza (E.T.), 71013 San Giovanni Rotondo, Italy; and Department of Clinical Science, University La Sapienza (E.T.), 00161 Rome, Italy

Address all correspondence and requests for reprints to: Alessandro Doria, M.D., Ph.D., Section on Genetics, Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215. E-mail: . alessandro.doria{at}joslin.harvard.edu

Abstract

Resistin is a newly identified hormone secreted by adipocytes that inhibits insulin action on peripheral tissues. The aim of our study was to investigate whether genetic variability at this locus is associated with the risk of type 2 diabetes. By sequencing 32 subjects with type 2 diabetes, we identified 8 single nucleotide polymorphisms (SNPs) in the 5'-flanking region and introns of the resistin gene. Allele and genotype distributions were determined for all 8 SNPs in 312 cases with type 2 diabetes and 303 nondiabetic controls, all of Caucasian origin. No significant association with type 2 diabetes was found at any of the polymorphic loci. However, an interactive effect of genotype at SNP 6 (IVS2 + 181GA) and obesity was a significant determinant of type 2 diabetes risk in this population. The relative risk of diabetes for the A/A genotype was 4.8 (95% confidence interval, 1.1–21.0) in individuals above the median for body weight, but only 0.7 (95% confidence interval, 0.2–2.1) in those below the median. This difference between relative risks was significant (² = 4.5; P = 0.03). A similar, but much weaker, interaction with obesity was observed for SNPs in linkage disequilibrium with SNP6. In conclusion, resistin does not appear to be a major gene for type 2 diabetes. However, our data suggest a synergistic effect of sequence differences at the resistin locus and obesity on risk of type 2 diabetes. Further studies are needed to confirm this finding in other populations.

This article has been cited by other articles:

				M.-F. Hivert, A. K. Manning, J. B. McAteer, J. Dupuis, C. S. Fox, L. A. Cupples, J. B. Meigs, and J. C. Florez Association of Variants in RETN With Plasma Resistin Levels and Diabetes-Related Traits in the Framingham Offspring Study Diabetes, March 1, 2009; 58(3): 750 - 756. [Abstract] [Full Text] [PDF]

				I Pantsulaia, G Livshits, S Trofimov, and E Kobyliansky Genetic and environmental determinants of circulating resistin level in a community-based sample Eur. J. Endocrinol., January 1, 2007; 156(1): 129 - 135. [Abstract] [Full Text] [PDF]

				C. Menzaghi, A. Coco, L. Salvemini, R. Thompson, S. De Cosmo, A. Doria, and V. Trischitta Heritability of Serum Resistin and Its Genetic Correlation with Insulin Resistance-Related Features in Nondiabetic Caucasians J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2792 - 2795. [Abstract] [Full Text] [PDF]

				C. Graveleau, V. G. Zaha, A. Mohajer, R. R. Banerjee, N. Dudley-Rucker, C. M. Steppan, M. W. Rajala, P. E. Scherer, R. S. Ahima, M. A. Lazar, et al. Mouse and Human Resistins Impair Glucose Transport in Primary Mouse Cardiomyocytes, and Oligomerization Is Required for This Biological Action J. Biol. Chem., September 9, 2005; 280(36): 31679 - 31685. [Abstract] [Full Text] [PDF]

				C. Kurlawalla-Martinez, B. Stiles, Y. Wang, S. U. Devaskar, B. B. Kahn, and H. Wu Insulin Hypersensitivity and Resistance to Streptozotocin-Induced Diabetes in Mice Lacking PTEN in Adipose Tissue Mol. Cell. Biol., March 15, 2005; 25(6): 2498 - 2510. [Abstract] [Full Text] [PDF]

				J. H. Lee, J. L. Chan, N. Yiannakouris, M. Kontogianni, E. Estrada, R. Seip, C. Orlova, and C. S. Mantzoros Circulating Resistin Levels Are Not Associated with Obesity or Insulin Resistance in Humans and Are Not Regulated by Fasting or Leptin Administration: Cross-Sectional and Interventional Studies in Normal, Insulin-Resistant, and Diabetic Subjects J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4848 - 4856. [Abstract] [Full Text] [PDF]

				S. R. Smith, F. Bai, C. Charbonneau, L. Janderova, and G. Argyropoulos A Promoter Genotype and Oxidative Stress Potentially Link Resistin to Human Insulin Resistance Diabetes, July 1, 2003; 52(7): 1611 - 1618. [Abstract] [Full Text] [PDF]

				M.-S. Tan, S.-Y. Chang, D.-M. Chang, J. C.-R. Tsai, and Y.-J. Lee Association of Resistin Gene 3'-Untranslated Region +62G->A Polymorphism with Type 2 Diabetes and Hypertension in a Chinese Population J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1258 - 1263. [Abstract] [Full Text] [PDF]