SINGLE NUCLEOTIDE POLYMORPHISMS AS PROGNOSTIC TOOL TO DIAGNOSE ADVERSE DRUG REACTIONS (ADR) AND DRUG EFFICACY

摘要

The invention provides diagnostic methods and kits including oligo and/orpolynucleotides or derivatives, including as well antibodies determiningwhether a human subject is at risk of getting adverse drug reaction afterstatin therapy or whether the human subject is a high or low responder or agood a or bad metabolizer of statins. The invention provides furtherdiagnostic methods and kits including antibodies determining whether a humansubject is at risk for a cardiovascular disease. Still further the inventionprovides polymorphic sequences and other genes. The present invention furtherrelates to isolated polynucleotides encoding a phenotype associated (PA) genepolypeptide useful in methods to identify therapeutic agents and useful forpreparation of a medicament to treat cardiovascular disease or influence drugresponse, the polynucleotide is selected from the group comprising: SEQ ID 1-131 with allelic variation as indicated in the sequences section contained ina functional surrounding like full length cDNA for PA gene polypeptide andwith or without the PA gene promoter sequence. Sequences: The sequence sectioncontains all phenotype associated (~PA~) SNPs and adjacent genomic sequences.The position of the polymorphisms that were used for the association studies(~baySNP~) is indicated. Sometimes additional variations are found in thesurrounding genomic sequence, that are marked by it~s respective IUPAC code.Although those surrounding SNPs were not explicitly analyzed, they likelyexihibit a similar association to a phenotype as the baySNP (due to linkagedisequillibrium, Reich D.E. et al. Nature 411, 199-204, 2001).