The adiponectin gene SNP+45 is associated with coronary artery disease in Type 2 (non-insulin-dependent) diabetes mellitus.
BACKGROUND
The ACRP30/adiponectin gene on chromosome 3q27, a region linked to the metabolic syndrome, encodes for the abundant adipocyte-specific secreted protein. Consistent rodent and human studies suggested that this adipokine may be a molecular link between metabolic and cardiovascular diseases.


OBJECTIVE
In order to investigate the role of single nucleotide polymorphisms (SNPs) within the APM1 gene in the susceptibility to coronary artery disease (CAD), we performed a case-control study on Caucasian Type 2 (non-insulin-dependent) diabetic patients, a population at high-risk for CAD.


METHODS
Five APM1 SNPs were genotyped in 162 Type 2 diabetic French and Swiss subjects with CAD and in 315 Type 2 diabetic French and Swiss subjects without CAD.


RESULTS
In univariate analysis, SNP+45 T>G was associated with CAD (OR 1.9 95% CI 1.2-2.9 P = 0.0036). In multivariate analysis, SNP+45 T>G remained associated with CAD (OR 1.2 95% CI 0.8-1.9 P = 0.017), independently of classical cardiovascular risk factors including components of the metabolic syndrome. SNP haplotype analyses revealed a CAD protective combination of all SNP wild-type alleles (OR 0.5 95% CI 0.3-0.7 P = 0.0006).


CONCLUSIONS
Our study, performed in diabetic subjects, revealed an association between individual SNP+45 in the APM1 gene and CAD. Furthermore, the susceptibility for CAD due to SNP+45 was independent of classic cardiovascular risk factors. Further studies will be necessary to confirm the role of SNP+45 in the development of CAD. However, ACRP30/adiponectin may contribute to atherosclerosis susceptibility in high-risk populations such as Type 2 diabetic subjects.
Lacquemant
C
C
Genomics Medicine Department and the Hammersmith Genome Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Froguel
P
P
Lobbens
S
S
Izzo
P
P
Dina
C
C
Ruiz
J
J
D052242:Adiponectin; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins