Association of the human adiponectin gene and insulin resistance

• Published in: European journal of human genetics : EJHG Vol. 12; no. 3; pp. 199 - 205
• Main Authors: FILIPPI, Emanuela, SENTINELLI, Federica, TRISCHITTA, Vincenzo, ROMEO, Stefano, ARCA, Marcello, LEONETTI, Frida, DI MARIO, Umberto, BARONI, Marco Giorgio
• Format: Journal Article
• Language: English
• Published: Avenel, NJ Nature Publishing 01.03.2004; Nature Publishing Group
• Subjects: Adipocytes; Adiponectin; Base Sequence; Biological and medical sciences; Body Mass Index; Cardiovascular disease; Diabetes; Female; Gene expression; General aspects. Genetic counseling; Genetics; Glucose; Guanine; Haplotypes; Homeostasis; Humans; Hypertension; Insulin; Insulin - blood; Insulin resistance; Insulin Resistance - genetics; Insulin Resistance - physiology; Intercellular Signaling Peptides and Proteins; Lipoproteins; Male; Medical genetics; Medical sciences; Metabolic syndrome; Middle Aged; Molecular Sequence Data; Obesity; Plasma; Polymorphism, Single Nucleotide - genetics; Product differentiation; Proteins; Proteins - analysis; Proteins - genetics; Single-nucleotide polymorphism; Thymine; Italy; Resistance; Association; Gene; Insulin human
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/sj.ejhg.5201120

Adiponectin is an adipocyte-secreted protein that modulates insulin sensitivity and whose low circulating concentration is associated with insulin resistance. In the present study, we analysed the association between two single-nucleotide polymorphisms (SNPs) in the adiponectin gene and insulin resistance in 253 nondiabetic subjects. In addition, we investigated whether this association is modulated by body mass index (BMI) levels. The SNPs +45T>G and +276G>T in the human adiponectin gene were detected in real-time PCR with LightCycler. No association was found with the +45T>G SNP. The +276G>T SNP was associated with higher BMI (P<0.01), plasma insulin (P<0.02) and HOMA(IR) (P<0.02). To analyse the possible interaction between BMI and the adiponectin gene on insulin resistance, the study group was divided into two subgroups, according to the BMI below or above the median of 26.2 kg/m(2). In both subgroups, subjects carrying the +276G>T SNP had higher HOMA(IR); however, the difference was highly significant among leaner (P<0.001), but not among heavier individuals, indicating that BMI status and the adiponectin gene interact in modulating insulin resistance. Among individuals with BMI <26.2 kg/m(2), the relative risk of insulin resistance was 9.7 (CI: 1.32-87.7, P<0.035). In a subgroup of 67 subjects, carriers of the +276G>T SNP had significantly (P<0.05) lower mean serum adiponectin levels (25.7 ng/ml) compared to noncarriers (37.0 ng/ml), suggesting a possible influence of the +276G>T SNP on adiponectin levels. In summary, we observed an association between the +276G>T SNP in the adiponectin gene and insulin resistance. In particular, among leaner individuals, the adiponectin gene appears to determine an increased risk to develop insulin resistance.