Abstract
The Affymetrix DMETTMM plus platform (Affymetrix, Santa Clara, CA, USA) is a GeneChip where 1936 SNPs can be genotyped in any given sample at once. The 1936 SNPs were distributed cross 225 genes in the genome. Thirtynine genes on the chip belong to phase I–II drug metabolism, disposition and drug transport gene family. These genes are functional in metabolizing the most widely prescribed anticancer drugs in the world including aromatase inhibitors, tamoxifen and thiopurines groups. In a high-throughput GeneChip array which is based on hybridization with allelespecific probes; genotyping errors are very common which limits the technologies applications; in addition missing calls for many SNPs on the chip immerge as a bigger and more serious problem in high- throughput genotyping methods. This study focuses on re-genotyping these No-call genotypes to maintain sample sizes that are already genotyped by Affymetrix DMETTMM plus platform. Sixty six different variations were identified, 39 of them had No-call genotypes; our re-genotyping resulted in increasing calling rate from 89.08% to 95.56%. Furthermore, Among the variations that were identified, 8 were non-reported: C.-209T > G in UGT2B7 and -698°C > A in CYP1A2 as promoter variants, c.252G > T in SLC22A6 and c.1356T > C in SLC15A1 as silent mutation, c.1277 + 69°C > T and c.1277 + 82°C > T in SLC22A1 as intronic variants associated with each other and the most important variations are two missense (non- synonymous) in NAT2 gene: D20N c.58G > A and G11S c.31G > A. Affymetrix DMETTMM plus platform.
Highlights
The therapeutic efficacy of most drugs is influenced by a number of different factors that in part include age, weight and concurrent drug use [1]
Jordanian individuals donated blood samples to be used as a probe for Affymetrix® DMETTMM plus platform (Affymetrix®, Santa Clara, CA, USA); with the aims of determine the pharmacogenomics of ADME genes profile in the Jordanian population
Sixty six variants were detected (39 single nucleotide polymorphism (SNP) of them are No-call target). These SNPs and others used to complete the missing genotype and/or to validate the Affymetrix® GeneChip
Summary
The therapeutic efficacy of most drugs is influenced by a number of different factors that in part include age, weight and concurrent drug use [1]. These factors may vary between patients [2]. The vast majority of the enzymes involved in drug metabolism are highly polymorphic [4] and allele frequencies of low-activity variants often differ by population [5]. Drugs may be metabolized more slowly in individuals who are carriers of a genetic polymorphism that results in a decreased or null activity of a given enzyme These individuals are at particular risk for adverse drug reactions (ADRs) or therapeutic failure [6]. Determined variation impacts drugs with narrow therapeutic indices, increasing the risk for the development of ADRs [7]
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