Program Nr: 2274

Evaluating resistin as a susceptibility gene for type 2 diabetes in the Finnish population. K. Silander1, C.M. Steppan2, K.L. Mohlke1, K.N. Lazaridis1, T.T. Valle3, T.A. Buchanan4, R.M. Watanabe4, M. Boehnke5, J. Tuomilehto3, R.N. Bergman4, M.A. Lazar2, F.S. Collins1. 1) National Human Genome Research Institute, NIH, Bethesda, MD; 2) Dept. of Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA; 3) Dept. of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland; 4) Dept. of Medicine, Dept. of Preventive Medicine, and Dept. of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA; 5) Dept. of Biostatistics, University of Michigan, Ann Arbor, MI.
   Resistin, a hormone secreted by adipocytes, has been suggested to play a role in insulin resistance in mice (Steppan et al. 2001, Nature 409:307-312). The Finland-United States Investigation of NIDDM genetics (FUSION) study aims to identify genetic factors contributing to type 2 diabetes. To evaluate whether genetic variants in human resistin are associated with type 2 diabetes we screened a cohort of 64 unrelated Finnish patients for possible gain-of-function variants. We also assessed possible association with insulin sensitivity by screening a cohort of 35 obese insulin-sensitive individuals for loss-of-function variants. These individuals were selected from a sample of approximately 600 unaffected individuals based on the criteria of having a BMI > 30 kg/m2 and a minimal model insulin sensitivity index > 0.53 min-1/pM. The controls were 14 normoglycemic individuals at least 70 years old. The exons and promoter region of the human resistin gene were screened for variants using dHPLC followed by sequencing. Several polymorphic sites were identified in the promoter region, 5'-untranslated region, intron 3 and 3'-untranslated region. However, we did not detect any coding region variations either in diabetic patients or in any of the other subjects screened. Although no association was apparent, we are currently typing a larger set of control individuals for the polymorphisms identified to determine whether the allele frequencies differ among type 2 diabetics, obese insulin-sensitive individuals and elderly controls.