Short alleles of P-selectin glycoprotein ligand-1 protect against premature myocardial infarction

Background Atherosclerosis is an inflammatory disease resulting from an injury that leads to an increase in the adhesiveness and permeability of the endothelium to leukocytes or platelets. The selectin family plays a key role initiating the cascade of events. Recently, we have demonstrated the functional relevance of a variable number of tandem repeats polymorphism affecting the P-selectin glycoprotein ligand (PSGL-1). Neutrophils carrying short alleles exhibit a significantly lower capacity to bind activated platelets. These alleles consistently protect against transient ischemic attack. We sought to evaluate the role of this polymorphism in premature myocardial infarction because genetic risk factors have more relevance in the development of disease in young patients. Methods We genotyped 219 Caucasian patients who had suffered a premature myocardial infarction (Ml) (aged :! 45 years) and 594 control subjects from our Mediterranean area. The role of the PSGL-1 polymorphism was also evaluated according to the additional risk factors of age, sex, smoking history, hypertension, hypercholesterolemia, and diabetes. Results The frequency of the short alleles (B and C) was significantly lower in patients than in controls (P =.012, odds ratio 0.62; 95% Cl 0.42-0.92). Multiple regression analysis revealed that B and C alleles had an independent protective effect on the development of premature MI (P =.034, odds ratio 0.62 95%Cl: 0.40-0.96). Conclusions we found an interesting association between a functional polymorphism and the risk of MI at a younger age. According to our results, the short B and C PSGL-1 alleles might protect against premature Ml, probably because of their lesser adhesive capacity.