55,56 Similarly, a Olaparib susceptibility locus for schizophrenia on chromosomal region 6p22, which was first, identified by linkage analysis in families, was recently confirmed by SNP haplotype analysis.57 Although results have been slow in coming, in practice, LD association mapping has identified susceptibility loci for both psoriasis and migraine.29,58 The hypothesis is that, in a similar way, haplotypes will be associated with particular drug responses. The concept, Inhibitors,research,lifescience,medical of using SNPs to develop an SNP profile is illustrated in Figure 1. Figure
1. Single nucleotide polymorphisms (SNPs): from a single SNP to an SNP profile. Genetic testing in the future: new technology There is a general tendency in human genetics to move away from studies of single genes to genome-wide approaches. The genetic testing for inherited disorders is following the same trend and, similarly,
the emphasis in testing for drug response will move from the analysis of single genes Inhibitors,research,lifescience,medical affecting drug metabolism, to the large-scale analysis of genetic variation in relation to drug response. Instead of investigating polymorphisms close to candidate genes, thousands of variants (SNPs) across the genome will be Inhibitors,research,lifescience,medical typed and organized into an individual “fingerprint,” also referred to as an SNP print12 or, for the sake of this review, an SNP pharmacogenetic profile. Multiple, closely ordered polymorphisms, Inhibitors,research,lifescience,medical which are inherited together over many generations and are therefore in LD, will distinguish particular regions of the genome. The objective will be to rapidly identify a genetic profile that characterizes patients who are more likely to suffer an ADR, compared with other patients who are likely to respond to the drug safely. There are various factors that
can confound such analyses, one very important, consideration being ethnic differences between patients. The allele frequencies Inhibitors,research,lifescience,medical of DNA polymorphisms such science as SNPs are highly variable between populations, so that population admixture may mask, blur, or alter the LD patterns.59 Secondly, ethnic variation in drug response is well known: in World War II it was discovered that. African-American soldiers who were treated with the antimalarial drug primaquine developed hemolytic anemia crises at high altitudes, due to glucose-6-phosphate dehydrogenase deficiency.36 Hence, different SNP profiles relating to drug response can be expected in different populations. This concept, is not new to genetic testing, for example, mutation analysis for cystic fibrosis is already tailored to patients with different, ethnic backgrounds.60 Essential to this progress is a scaling up of the applied technology, and this is happening rapidly.