Association of the H2 haplotype of the P2Y12 receptor with an increased risk for thrombosis and peripheral arterial disease

摘要

An in vitromethod for determining a risk of developing thrombosis in a subject or the sensitivity of a subject toward a thienopyridine therapy, comprises identifying polymorphisms of P2Y 12receptor at positions 139, 744, and 801 of the intron (comprising a sequence of 947 bp, SEQ ID NO: 1), and at position 52 of exon 2 (comprising a sequence of 130 bp, SEQ ID NO: 2), is new. The simultaneous presence of T and C at position 139 and 744 of the intron, respectively, insertion of A at position 801 of the intron, and presence of T at position 52 of exon 2 are designated H2 haplotype, and when present on at least one allele indicates a higher risk to develop thrombosis in comparison with a control subject without any H2 allele, or indicates a lower sensitivity of the subject toward a thienopyridine therapy in comparison with a control subject without any H2 allele. Independent claims are also included for: (1) an in vitromethod for identifying at least one polymorphism of a haplotype of the P2Y 12receptor associated with thrombosis in a subject or associated with lower sensitivity toward a thienopyridine therapy; (2) an isolated nucleic acid encoding the P2Y 12receptor, comprises the P2Y 12gene sequence with the simultaneous presence of T and C at positions 139 and 744 of the intron, respectively, insertion of A at position 801 of the intron, and presence of T at position 52 of exon 2; and (3) a kit for performing the methods above, comprising a pair of nucleotide primers specific for amplifying all or part of the P2Y 12gene comprising at least one of positions 139, 744 and 801 of the intron (SEQ ID NO: 1) and/or position 52 of exon 2 (SEQ ID NO: 2).