Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriers of the Thr-87 variant of the ATP receptor P2Y11.

Abstract

Extracellular ATP acting on the P2Y11 receptor regulates inflammatory cells. We hypothesized that polymorphisms in the receptor could influence the risk of acute myocardial infarction (AMI). In the Malmö diet and cancer AMI case-control study (n = 3732) the P2Y11 gene Thr-87 polymorphism was present in 19.8% of the controls and 22.9% in AMI patients (OR 1.21; P = 0.03). Stronger associations were found in patients with family history (FH) of AMI, 1.32; early-onset (EO) AMI, 1.43; or EO AMI combined with FH, 1.50; supporting a genetic mechanism. The Thr-87 homozygotes had an even greater risk of AMI, 1.94 (P = 0.04); and 2.48 in the EO AMI subgroup, suggesting a genetic dosage effect. In the cardiovascular risk factor group (n = 6055), 21.3% carried the Thr-87 allele. C-reactive protein was elevated in Thr-87 carriers: 1.6 mg/L vs. 1.3 mg/L (P = 0.001). No difference was seen for blood pressure, lipids, body mass index, smoking, or diabetes mellitus. The common Ala-87-Thr polymorphism of the P2Y11 receptor is associated with AMI and increased levels of C-reactive protein. We hypothesize that an inflammatory mechanism might be involved. The P2Y11 receptor is a promising new drug target in the prevention of AMI.