Association of the human adiponectin gene and insulin resistance.
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.
Filippi
Emanuela
E
1Department of Clinical Sciences, Division of Endocrinology, University of Rome La Sapienza, Rome, Italy.
Sentinelli
Federica
F
Trischitta
Vincenzo
V
Romeo
Stefano
S
Arca
Marcello
M
Leonetti
Frida
F
Di Mario
Umberto
U
Baroni
Marco Giorgio
MG
D052242:Adiponectin; D001483:Base Sequence; D015992:Body Mass Index; D005260:Female; D006147:Guanine; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D013941:Thymine
D052242:Adiponectin; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D006147:Guanine; D013941:Thymine