The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population

Table 1 The list and characteristics of variants analyzed in the current Emirati cohort

Gene	SNP ID & sub	Synonym	Type	Potential clinical effect*	Clinical annotation Level of evidence (PharmGKB)	References
CYP2C19	rs4244285 (c.681G > A)	CYP2C19*2	Synonymous Splice variant	Decrease bioavailability (LoF variant). Increase MACE	Level 1A	[11, 19]
CYP2C19	rs4986893 (c.636G > A)	CYP2C19*3	Stop gained	Decrease bioavailability (LoF variant). Increase MACE	Level 1A	[19, 20]
CYP2C19	rs12248560 (c.-806C > T)	CYP2C19*17	Intronic variant on the 5’ flanking region	Increase bioavailability (GoF variant)	Level 1A	[19, 21]
CYP2C19	rs12769205 (12662A > G)	CYP2C192/35	Synonymous splice variant	Decrease bioavailability. Increase MACE	Level 1A	[19]
ABCB1	rs1045642 (c.3435 T > C)	C3435T	synonymous variant	Decrease bioavailability, drug response, Increase MACE	Level 3	[22]
ABCB1	rs2032582 (c.2677G > T)	G2677T	Missense variant	Decrease bioavailability, drug response, Increase MACE	Level 3	[23]
ABCB1	rs1128503 (c.C123)	C123T	Missense variant	Decrease bioavailability, drug response, Increase MACE	Level 3	[23]
PON1	rs662 (c.575A > G)	Q192R	Missense variant	Increase paraoxonase activity. Increase MACE	Level 4	[24]
PON1	rs854560	L55M	Missense variant	Decrease the serum concentration of paraoxonase enzyme	Level 4	[25]
P2Y12R	rs6785930 (c.18C > T)	C34T	Missense variant	Reduce response to clopidogrel. Increase MACE	Level 4	[26]
P2Y12R	rs6809699	G52T	Synonymous variant	Increase clopidogrel resistance	Level 3	[27]

*Potential clinical effect based upon PharmGKB database
SNP, Single Nucleotide Polymorphism; CYP, Cytochrome P; ABCB1, ATP-binding Cassette Subfamily B Member 1; LoF, Loss Of Function; GoF, Gain Of Function; MACE, Major Adverse Cardiovascular Events; PON1, Paraoxanase 1; P2Y12R, Purnegic PY12 Receptor

ISSN: 1479-7364