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An ATG Repeat in the 3'-Untranslated Region of the Human Resistin Gene Is Associated with a Decreased Risk of Insulin Resistance

Department of Experimental Medicine and Pathology, CSS-Mendel Institute (A.P., A.A., M.B., B.D.), Department of Clinical Science (V.T.), University La Sapienza, 00100 Rome, Italy; Unit of Endocrinology, Scientific Institute Casa Sollievo Sofferenza Hospital (R.D.P., A.R., V.T.), 71013 San Giovanni Rotondo (Foggia), Italy; and Institute of Internal Medicine, Endocrine and Metabolic Diseases, University of Catania, Garibaldi Hospital (R.B., R.V., L.F.), 95123 Catania, Italy

Address all correspondence and requests for reprints to: Lucia Frittitta, Ph.D., M.D., Endocrinologia, Ospedale Garibaldi, Piazza S. M. di Gesù, 95123 Catania, Italy. E-mail: ; or Antonio Pizzuti, Ph.D., M.D., Istituto CSS-Mendel, Viale Regina Margherita, 261, 00198 Rome, Italy. E-mail: . antpizzuti{at}libero.it

Abstract

Resistin is overexpressed in human adipose tissue of obese individuals and is likely to modulate insulin sensitivity. Resistin is, therefore, a candidate gene for insulin resistance. We searched for polymorphisms in the resistin gene by single strand conformation polymorphism and direct sequencing. An ATG triplet repeat in the 3'-untranslated region was identified and considered for association with insulin resistance. Three alleles were identified (allele 1: 8 repeats, allele frequency, 0.3%; allele 2: 7 repeats; allele frequency, 94.5%; allele 3: 6 repeats; allele frequency, 5.2%). Two hundred and three unrelated white Caucasian nondiabetic subjects from Sicily and 456 from the Gargano area (center east coast of Italy) were analyzed. Among Sicilians, subjects carrying allele 3 had a lower fasting insulin and insulin resistance index (homeostasis model assessment of insulin resistance; P < 0.001 for both) and glucose (P = 0.025) and insulin (P = 0.002) levels during the oral glucose tolerance test. In subjects from Gargano, those carrying allele 3 had lower fasting plasma glucose levels and serum triglycerides (P = 0.01 for both). When the 2 populations were analyzed together, subjects carrying allele 3 had lower fasting insulin levels (P < 0.005), homeostasis model assessment of insulin resistance (P < 0.005), and serum triglycerides (P = 0.01).

In conclusion, our data suggest that subjects carrying allele 3 of the resistin gene are characterized by relatively high insulin sensitivity.

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