The Coriell personalized medicine collaborative pharmacogenomics appraisal, evidence scoring and interpretation system

Table 4 Genotype-phenotype drug response interpretations of the Pharmacogenomics Advisory Group-approved drug-gene pairs proton pump inhibitors and CYP2C19 ^a

Common diplotypes^b	Expected population frequency, %^c			PK/PD phenotype	Clinical phenotype	FDA guidelines
Common diplotypes^b	Caucasian ancestry	African ancestry	East Asian ancestry	PK/PD phenotype	Clinical phenotype	FDA guidelines
CYP2C191/1	38	35	35	EM: normal enzymatic function and normal drug elimination	Likely to have normal response to standard dose of PPIs	–
CYP2C191/2, CYP2C191/8, CYP2C192/17, and other rare diplotypes (see Additional file 1: Table S7)	26	31	48	IM: reduced enzymatic function leading to reduced drug elimination and greater drug exposure	Both IM and PM likely to have improved PPI efficacy at standard dose of PPI as measured by intragastric pH, duration of inhibition, and cure rates for GERD and Helicobacter pylori	–
CYP2C192/2 and other rare diplotypes (see Additional file 1: Table S7)	2	3.5	15	PM: greatly reduced or abolished enzymatic function, leading to reduced drug elimination and greater drug exposure		–
CYP2C1917/17	5	4.5	0.04	UM: enhanced enzymatic function leading to greater drug elimination and reduced drug exposure	Decreased PPI efficacy at standard doses	–
CYP2C191/17	29	26	2	Unk: metabolizer status undetermined and therefore unknown; PD data shows platelet response is intermediate between IMs and EMs	Unknown effect on drug response

Abbreviations: EM Extensive metabolizer, FDA Food and Drugs Administration, GERD gastroesophageal reflux disease, IM intermediate metabolizer, PD pharmacodynamic, PK pharmacokinetic, PM poor metabolizer, PPI proton pump inhibitors, UM Ultra-rapid metabolizer, Unk metabolizer status unknown.
^aSupporting evidence may be found in Additional file 2: Section S2.0-2.7, and Additional file 1: Tables S5 and S7. These include summaries of the PhAESIS evaluation and referenced publications supporting the drug-gene clinical phenotypes.
^bDiplotypes with frequencies of less than 0.4% in Caucasians are included above. Other rare diplotypes that fall under the same phenotype category can be found in the genotype-phenotype Punnett table (see Additional file 1: Table S7). Diplotypes above and in the genotype-phenotype Punnett table include both clinically validated genetic results (those that include variants with evidence code 1) and results that include variants with evidence scores 2 to 7 (potentially clinically relevant). The latter require further validation to support their inclusion for clinical reporting.
^cPopulation frequencies are estimated based on reported gene variant allele frequencies (see Additional file 1: Table S6) and Hardy-Weinberg principles.

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