An ATG repeat in the 3'-untranslated region of the human resistin gene is associated with a decreased risk of insulin resistance.
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.
Pizzuti
Antonio
A
Department of Experimental Medicine and Pathology, CSS-Mendel Institute, University La Sapienza, 00100 Rome, Italy. antipuzzuti@libero.it
Argiolas
Alessandra
A
Di Paola
Rosa
R
Baratta
Roberto
R
Rauseo
Anna
A
Bozzali
Maura
M
Vigneri
Riccardo
R
Dallapiccola
Bruno
B
Trischitta
Vincenzo
V
Frittitta
Lucia
L
D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006729:Hormones, Ectopic / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D007558:Italy; D008297:Male; D011110:Polymorphism, Genetic; D052243:Resistin; D012307:Risk Factors; D018911:Trinucleotide Repeats
D020413:3' Untranslated Regions; D017931:DNA Primers; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D052243:Resistin