Influence of CYP450 Enzymes and ABCB1 Polymorphisms on Clopidogrel Response in Moroccan Patients with Acute Coronary Syndromes

Figures & data

Table 1 Alleles and Variations Detected by the GenoChip CYP+ Array

Genes	Allele	Variation	rs Number
CYP1A2	*1C	−3860G>A	rs2069514
	*1F	−163C>A	rs762551
CYP2B6	*6	516G>T	rs3745274
	*6	785A>G	rs2279343
CYP2C9	*2	430C>T	rs1799853
	*3	1075A>C	rs1057910
CYP2C19	*2	430C>T	rs4244285
	*3	1075A>C	rs4986893
	*17	−806C>T	rs12248560
CYP3A4	*1B	−392A>G	rs2740574
	*22	15389C>T	rs35599367
CYP3A5	*2	27289C>A	rs28365085
	*3	6986A>G	rs776746

Table 2 Baseline Characteristics of Patients

Characteristic	Total (n = 55)	Clopidogrel Responder (n = 36)	Clopidogrel Non-Responder (n = 19)	P_value
Age, yrs	58.47±8.67	57.5±9.3	60.4±7.1	0.2
Men. N (%)	42 (76.4)	30 (83.3)	12 (63.2)	0.1
Body Weight, kg	72.24±12.16	72.03±12.98	72.52±11.20	0.9
Umbilical waist, Cm	94.87±14.52	94.03±12.83	96.04±16.83	0.6
BMI, kg/m2	26.49±4.6	26.25±4.5	26.95±4.9	0.6
Cardiovascular risk factors, n (%)
Diabetes mellitus	21 (38.2)	11 (30.6)	10 (52.6)	0.1
Hypertension	14 (25.5)	8 (22.2)	6 (31.6)	0.6
Smoking	34 (61.8)	23 (63.9)	11 (57.9)	1
Dyslipidemia	5 (9.1)	3 (8.3)	2 (10.5)	1
Platelets, 10^3/μL	233.109±70.382	230.750±62.120	237.579±85.579	0.7
STEMI, n (%)	15 (27.3)	12 (80)	3 (20)	0.042
GRACE score	124.22±32.98	125.9±34.7	121.1±30.2	0.6
In-hospital treatment, n (%)
Enoxaparin	49 (89.1)	32 (88.9)	17 (89.5)	1
Statin	52 (94.5)	34 (94.4)	18 (94.7)	1
PPI	8 (14.5)	4 (11.1)	4 (21.1)	0.4
AEC inhibitor	21 (38.2)	14 (38.9)	7 (36.8)	0.9
Beta blocker	26 (47.3)	16 (44.4)	10 (52.6)	0.5

Abbreviations: BMI, body mass index; STEMI, ST-elevation myocardial infarction; PPI, proton pump inhibitors; AEC inhibitor, angiotensin-converting enzyme inhibitor.

Table 3 Distribution of Genotype and Allele Prevalence in the Study Population

Genotype SNP	Population n=55
	No (%)
CYP1A2
*1/*1	6(10.9%)
*1/*1F	24(43.6%)
*1F/*1F	14(25.5%)
*1C/*1F	11(20%)
CYP2B6 (516G>T)
GG	35(63.6%)
GT	20(36.4%)
CYP2B6 (785A>G)
AA	35(63.6%)
AG	20(36.4%)
CYP2C9
*1/*1	49(89.1%)
*1/*2	6(10.9%)
CYP2C19
*1/*1	40(72.7%)
*1/*17	15(27.3%)
CYP3A4
*1/*1	36(65.5%)
*1/*1B	19(34.5%)
CYP3A5
*1/*3	15(27.3%)
*3/*3	40(72.7%)
ABCB1 C3435T
CC	21(38.2%)
CT	29(52.7%)
TT	5(9.1%)

Table 4 Genotype/ Phenotype Distribution of the Studied Genes According to Clopidogrel Responder and Non-Responder Groups

Gene	Genotype/Phenotype	Clopidogrel Responder n=36	Clopidogrel Non-Responder n=19	P value
		No (%)	No (%)
ABCB1 C3435T				0.057
	WT (n = 21)	17 (47.2%)	4 (21.1%)
	T carriers (n = 34)	19 (52.8%)	15 (78.9%)
CYP1A2				1
	NM/RM (n = 41)	27 (75%)	14 (73.7%)
	UM (n = 14)	9 (25%)	5 (26.3%)
CYP2B6				0.8
	IM/NM (n = 42)	28 (77.8%)	14 (73.7%)
	PM (n = 13)	8 (22.2%)	5(26.3%)
CYP2C9				1
	NM (n = 49)	32 (88.9%)	17 (89.5%)
	IM (n = 6)	4 (11.1%)	2 (10.5%)
CYP2C19				1
	NM (n = 40)	26 (72.2%)	14 (73.7%)
	UM (n = 15)	10 (27.8%)	5 (26.3%)
CYP3A4*1B (−392A>G)				0.4
	AA (n = 36)	25 (69.4%)	11 (57.9%)
	AG (n = 19)	11 (30.6%)	8 (42.1%)
CYP3A5				0.9
	Expressers (n = 15)	9 (28.1%)	5 (26.3%)
	Non-expressers (n = 40)	23 (71.9%)	14 (73.7%)

Note: Patients with aggregation >208 PRU were considered as clopidogrel non-responders.

Abbreviations: IM, intermediate metabolizer; NM, normal metabolizer; PM, poor metabolizer; RM, rapid metabolizer; UM, ultrarapid metabolizer; WT, wild type.