Abstract 4859: Genetic Polymorphism T45G on Adiponectin Gene Affects Cardiovascular Risk by Regulating Adiponectin Levels in Arterial Hypertension
Background: Evidence suggests that adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects, while it is inversely associated with obesity and the development of arterial hypertension. We examined the impact of T45G polymorphism on adiponectin gene, on the risk for coronary artery disease (CAD) and the expression of adipokines in heathy individuals and patients with CAD. We also examined its possible impact on the development of arterial hypertension.
Methods: We studied 214 pts with CAD and 147 healthy controls. Genetic polymorphism T45G was determined by PCR, while circulating adiponectin, resistin and leptin were determined by ELISA, under stable clinical conditions.
Results: The genotype distribution was different between CAD patients (GG: 5(2.3%) GT: 65(30.4%), TT:144(67.3%)) and controls (GG:2(1.4%), GT: 31(21.1%), TT:114(77.6%), p<0.05). The risk for CAD was OR[95%CI]:0.595[0.368 – 0.964], p=0.03 for 45TT vs 45GT+GG. Importantly, The 45TT homozygotes had lower risk of arterial hypertension (OR[95%CI]:0.439[0.270 – 0.713], p=0.001). The 45TT genotype was associated with higher adiponectin levels (13.1±1.14pg/ml) compared to 45GT+GG (8.30±2.17pg/ml, p<0.05) among healthy individuals, but not in CAD patients (13.67±0.97 vs 15.20±1.6pg/ml respectively, p=NS). Circulating resistin and leptin were not different between genotypes in the control group (6.88±0.40 and 13.6±0.85 in TT vs 6.16±0.65 pg/ml and 14.04±2.23 pg/ml in GT+GG, p=NS for both). In the CAD group, leptin levels were also similar between 45TT (15.2±1.8pg/ml) and 45GT+GG (14.1±3.2pg/ml, p=NS). Similarly, the 45TT genotype had similar resistin (5.9±0.3pg/ml) compared to 45GT+GG (7.69±0.81pg/ml, p=NS), in the CAD group.
Conclusions: The 45TT genotype of adiponectin gene is associated with lower risk of arterial hypertension and decreased cardiovascular risk. This genotype has a striking effect on adiponectin expression in healthy individuals, but not in CAD patients. Therefore, homozygosity for the 45T allele decreases the risk for CAD by increasing circulating levels of adiponectin in healthy individuals, while its functional effect is masked after the establishment of coronary atherosclerosis.