ABSTRACT
Aspirin prevents the production of thromboxane A2 (TXA2) by irreversibly inhibiting platelet cyclooxygenase, exhibiting antiplatelet actions. This agent has been reported to prevent relapse in patients with ischemic heart disease or cerebral infarction via this action mechanism. However, there are individual differences in this action, and aspirin is not effective in some patients, which is referred to as 'aspirin resistance'. In this study, we analyzed laboratory aspirin resistance by platelet aggregation in 110 healthy adult Japanese males using 24 single-nucleotide polymorphisms (SNPs) of nine genes involved in platelet aggregation/hemorrhage. Among SNPs involved in platelet aggregation, aspirin was less effective for 924T homozygote of a TXA2 receptor, 924T>C, and 1018C homozygote of a platelet membrane glycoprotein GPIbalpha, 1018C>T, suggesting that 924T and 1018C alleles are involved in aspirin resistance.
Subject(s)
Aspirin/pharmacology , Drug Resistance/genetics , Membrane Proteins/genetics , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Polymorphism, Single Nucleotide , Receptors, Thromboxane A2, Prostaglandin H2/genetics , Adult , Asian People , Aspirin/blood , Gene Frequency , Genotype , Humans , Japan , Male , Membrane Glycoproteins , Phenotype , Platelet Aggregation/genetics , Platelet Aggregation Inhibitors/blood , Platelet Glycoprotein GPIb-IX Complex , Reference Values , Salicylic Acid/blood , Thromboxane B2/bloodABSTRACT
The Cd(II) complex of a peptide, Z-Cys-Ala-Pro-His-OMe was prepared and characterized by absorption, CD, 1H-, 13C-, and 113Cd-nmr, and nuclear Overhauser effect spectroscopy (NOESY) spectra to show the coordination of cysteine thiolate and histidine imizazole to Cd(II) ion. The NOESY spectra in dimethyl formamide showed that the cysteine residue was in proximity to the histidine residue. These results reveal the chelation of Z-Cys-Ala-Pro-His-OMe to Cd(II) ion in solution. Temperature-dependent dissociation equilibrium of histidine imidazole in solution was observed in this complex. Structural features of the chelating peptide are discussed.