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.
Cardiovascular and Endocrine Department of the Scientific Institute, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. endocrino@operapadrepio.it
Simonetta
S
Bacci
Claudia
C
Menzaghi
Tonino
T
Ercolino
Xiaowei
X
Ma
Anna
A
Rauseo
Lucia
L
Salvemini
Carlo
C
Vigna
Raffaele
R
Fanelli
Umberto
U
Di Mario
Alessandro
A
Doria
Vincenzo
V
Trischitta
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