TPMT Gene Polymorphisms: On the Doorstep of Personalized Medicine (Commentary)
Since the initial human genome sequence has become available in 2001, sequence variability among individual genomes came into focus of the research in the field of human genetics. More than 99 per cent of the DNA sequence is identical among individuals. The remaining DNA is responsible for genetic diversity (1). Polymorphisms are common genetic variations in the human genome representing sequence variations that occur in 1 per cent of gene alleles in a given population. The most studied polymorphisms, SNPs (single nucleotide polymorphisms) were discovered thirty years ago. These are distributed over the whole genome. The number of SNPs is estimated to range from 0.5 to 1 SNP per 100 base pairs (bp). Besides SNPs, there are other important classes of polymorphisms, such as VNTRs (variable number of tandem repeats, polymorphic sequence containing 2050 copies of 6-100 bp repeats), STRs (short tandem repeats, a subclass of VNTR in which repeat unit consists of 2-7 bp) and copy number polymorphisms. Despite extensive studies of polymorphisms, among a myriad of “promising” genetic markers, only a few have been shown to be valid ones. There is no doubt that the thiopurine S-methyltransferase (TPMT) gene polymorphism is one of them. Moreover it is already successfully applied at the bedside as a powerful pharmacogenetic marker.