The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients.
OBJECTIVE
Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T>G and +276G>T) have been associated with low circulating adiponectin levels, insulin resistance, and type 2 diabetes. We investigated whether these genetic markers are determinants of coronary artery disease (CAD) in type 2 diabetic patients.


METHODS
A total of 376 consecutive type 2 diabetic patients were studied: 142 case subjects with coronary stenosis >50% or previous myocardial infarction and 234 control subjects with no symptoms, no electrocardiogram (ECG) signs of myocardial ischemia, and a normal ECG stress test (n = 189) and/or (n = 45) with coronary stenosis <or=50%.


RESULTS
No association with CAD was observed for the +45 SNP (P = 0.48). By contrast, a significant association was observed for the +276 SNP, with T/T homozygotes having a lower risk of CAD than carriers of other genotypes (adjusted odds ratio [OR] 0.13 [95% CI 0.037-0.46], P = 0.002). A similarly protective effect of the +276 T/T genotype was observed in 110 case and 45 control subjects for whom the CAD status had been determined by angiography (0.04 [0.006-0.30], P = 0.002). Serum adiponectin, although clearly related to several features of the proatherogenic/insulin-resistant phenotype, was not different between control subjects and CAD patients (26 +/- 17 vs. 25 +/- 13 microg/ml).


CONCLUSIONS
In conclusion, the +276 G>T polymorphism is a determinant of CAD risk in type 2 diabetic patients. This marker may assist in the identification of diabetic individuals at especially high risk of CAD, so that preventive programs can be targeted at these subjects.
Bacci
Simonetta
S
Cardiovascular and Endocrine Department of the Scientific Institute, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. endocrino@operapadrepio.it
Menzaghi
Claudia
C
Ercolino
Tonino
T
Ma
Xiaowei
X
Rauseo
Anna
A
Salvemini
Lucia
L
Vigna
Carlo
C
Fanelli
Raffaele
R
Di Mario
Umberto
U
Doria
Alessandro
A
Trischitta
Vincenzo
V
D052242:Adiponectin; D003327:Coronary Disease / Q000235:genetics*; D023921:Coronary Stenosis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012016:Reference Values
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins