Characterization of Reference Materials for CYP2C9, CYP2C19, VKORC1, CYP2C Cluster Variant, GGCX, and Other Pharmacogenetic Alleles with an Association for Molecular Pathology (AMP) Pharmacogenetics Working Group Tier 2 Status - A GeT-RM Collaborative Project.

Abstract Pharmacogenetic (PGx) testing is increasingly available from clinical and research laboratories. However, only a limited number of quality control and other reference materials (RMs) are currently available for many of the variants that are tested. The Association for Molecular Pathology PGx Work Group has published a series of papers recommending alleles for inclusion in clinical testing. Several of the alleles were not considered for Tier 1 due to a lack of reference materials. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention (CDC) based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 18 DNA samples derived from Coriell cell lines. DNA samples were distributed to five volunteer testing laboratories for genotyping using three commercially available and laboratory developed tests. Several Tier 2 variants including CYP2C9*13, CYP2C19*35, the CYP2C cluster variant (rs12777823), two variants in VKORC1 (rs61742245 and rs72547529) related to warfarin resistance and two variants in GGCX (rs12714145 and rs11676382) related to clotting factor activation were identified among these samples. These publicly available materials complement the pharmacogenetic reference materials previously characterized by GeT-RM and will support the quality assurance and quality control programs of clinical laboratories performing pharmacogenetic testing.