Integrin ß1 polymorphisms and bleeding risk after coronary artery stenting.

Bleeding complications following percutaneous coronary intervention associate with increased mortality. However, the underlying molecular mechanisms are insufficiently understood. Platelet recruitment and activation at sites of vascular injury depends on the function of integrin adhesion receptors. Besides GPIIbIIIa as the most abundant integrin receptor, platelets relevantly express ß1 integrins. Experimental evidence from in vivo studies suggests a significant role of ß1 integrins in primary haemostasis. However, little is known about the clinical impact of genetic alterations of the β1 subunit, which might contribute to bleeding complications in patients. In this study, we performed DNA sequencing of patients suffering from bleeding complications after coronary artery stenting according to TIMI or BARC classification. We isolated DNA samples from 741 patients out of a cohort from 14,160 patients recruited in seven randomized clinical trials between June 2000 and May 2011. Subsequently, Sanger sequencing was performed covering the β1 integrin cytoplasmic activation domain (exon16) and its non-coding upstream region. Out of 764 patients suffering from bleeding complications, 741 DNA samples were successfully sequenced. Genotype variation was detected for SNP rs2153875 located within the non-coding upstream region with following allele frequency in study population: CC (7.3%), CA (35%) and AA (57.8%), which is similar to a general population cohort. Further, genotype variation in SNP rs2153875 do not associate with the frequency of TIMI or BARC classified access or non-access site bleedings. Genotype variations of the β1 integrin activation domain do not associate with bleeding risk after PCI.      «

Bleeding complications following percutaneous coronary intervention associate with increased mortality. However, the underlying molecular mechanisms are insufficiently understood. Platelet recruitment and activation at sites of vascular injury depends on the function of integrin adhesion receptors. Besides GPIIbIIIa as the most abundant integrin receptor, platelets relevantly express ß1 integrins. Experimental evidence from in vivo studies suggests a significant role of ß1 integrins in primary h...     »