Differences in the Proportion of CYP2C19 Loss-of-Function Between Cerebral Infarction and Coronary Artery Disease Patients

Figures & data

Table 1 Clinical Characteristics of Patients Among Different Groups in This Study

	Total (n=1163)	Patients with CI (n=413)	Patients with CAD (n=509)	Patients with CI Complicated with CAD (n=241)	P values
Age, years
<65, n (%)	354 (30.4%)	145 (35.1%)	164 (32.2%)	45 (18.7%)	<0.001
≥65, n (%)	809 (69.6%)	268 (64.9%)	345 (67.8%)	196 (81.3%)
Gender
Male, n (%)	800 (68.8%)	279 (67.6%)	351 (69.0%)	170 (70.5%)	0.727
Female, n (%)	363 (31.2%)	134 (32.4%)	158 (31.0%)	71 (29.5%)
History of smoking, n (%)	253 (21.8%)	92 (22.3%)	128 (25.1%)	33 (13.7%)	0.002
History of alcohol consumption, n (%)	39 (3.4%)	17 (4.1%)	17 (3.3%)	5 (2.1%)	0.376
Hypertension, n (%)	799 (68.7%)	310 (75.1%)	309 (60.7%)	180 (74.7%)	<0.001
Diabetes, n (%)	374 (32.2%)	124 (30.0%)	161 (31.6%)	89 (36.9%)	0.179

Table 2 Frequencies of CYP2C19 636G>A and CYP2C19 681G>A Genotypes in All Subjects and Patients Among Different Groups

Genotype/Allele	Total (n=1163)	Patients with CI (n=413)	Patients with CAD (n=509)	Patients with CI Complicated with CAD (n=241)	P value
CYP2C19 636G>A
G/G	1055(90.7%)	382(92.5%)	450(88.4%)	223(92.5%)	0.096
G/A	104(8.9%)	31(7.5%)	56(11.0%)	17(7.1%)
A/A	4(0.3%)	0(0)	3(0.6%)	1(0.4%)
G	2214(95.2%)	795(96.2%)	956(93.9%)	463(96.1%)	0.041
A	112(4.8%)	31(3.8%)	62(6.1%)	19(3.9%)
HWE (χ^2, P)	χ^2=0.696, P=0.404	χ^2=0.628, P=0.428	χ^2=0.743, P=0.389	χ^2=1.132, P=0.287
CYP2C19 681G>A
G/G	555(47.7%)	176(42.6%)	279(54.8%)	100(41.5%)	0.001
G/A	502(43.2%)	191(46.2%)	192(37.7%)	119(49.4%)
A/A	106(9.1%)	46(11.1%)	38(7.5%)	22(9.1%)
G	1612(69.3%)	543(65.7%)	750(73.7%)	319(66.2%)	<0.001
A	714(30.7%)	283(34.3%)	268(26.3%)	163(33.8%)
HWE (χ^2, P)	χ^2=0.244, P=0.621	χ^2=0.294, P=0.588	χ^2=0.387, P=0.534	χ^2=2.562, P=0.109

Abbreviation: HWE, Hardy Weinberg Equilibrium.

Table 3 The Distributions of Different Genotypes’ Combinations and Metabolic Phenotypes of CYP2C19 in Different Groups

Genotype	Total (n=1163)	Patients with CI (n=413)	Patients with CAD (n=509)	Patients with CI Complicated with CAD (n=241)	P value
Genotypes
636G/G + 681G/G	481(41.4%)	155(37.5%)	237(46.6%)	89(36.9%)	0.006
636G/G + 681G/A	468(40.2%)	181(43.8%)	175(34.4%)	112(46.5%)
636G/A + 681 G/G	70(6.0%)	21(5.1%)	39(7.7%)	10(4.1%)
636G/G + 681A/A	106(9.1%)	46(11.1%)	38(7.5%)	22(9.1%)
636G/A + 681 G/A	34(2.9%)	10(2.4%)	17(3.3%)	7(2.9%)
636A/A + 681G/G	4(0.3%)	0(0)	3(0.6%)	1(0.4%)
Phenotypes
EM	481(41.4%)	155(37.5%)	237(46.6%)	89(36.9%)	0.035
IM	538(46.3%)	202(48.9%)	214(42.0%)	122(50.6%)
PM	144(12.4%)	56(13.6%)	58(11.4%)	30(12.4%)

Abbreviations: EM, Extensive metabolizer; IM, Intermediate metabolizer; PM, Poor metabolizer.

Table 4 Pairwise Comparison of CYP2C19 Genotypes and Metabolic Phenotypes Distribution Among Three Groups

Genotype	Patients with CAD (n=509)	Patients with CI (n=413)	P value	Patients with CAD (n=509)	Patients with CI Complicated with CAD (n=241)	P value	Patients with CAD (n=509)	Patients with CI and Patients with CI Complicated with CAD (n=654)	P value
Genotypes
636G/G + 681G/G	237(46.6%)	155(37.5%)	0.002	237(46.6%)	89(36.9%)	0.015	237(46.6%)	244(37.3%)	<0.001
636G/G + 681G/A	175(34.4%)	181(43.8%)		175(34.4%)	112(46.5%)		175(34.4%)	293(44.8%)
636G/A + 681 G/G	39(7.7%)	21(5.1%)		39(7.7%)	10(4.1%)		39(7.7%)	31(4.7%)
636G/G + 681A/A	38(7.5%)	46(11.1%)		38(7.5%)	22(9.1%)		38(7.5%)	68(10.4%)
636G/A + 681 G/A	17(3.3%)	10(2.4%)		17(3.3%)	7(2.9%)		17(3.3%)	17(2.6%)
636A/A + 681G/G	3(0.6%)	0(0)		3(0.6%)	1(0.4%)		3(0.6%)	1(0.2%)
Phenotypes
EM	237(46.6%)	155(37.5%)	0.022	237(46.6%)	89(36.9%)	0.043	237(46.6%)	244(37.3%)	0.006
IM	214(42.0%)	202(48.9%)		214(42.0%)	122(50.6%)		214(42.0%)	324(49.5%)
PM	58(11.4%)	56(13.6%)		58(11.4%)	30(12.4%)		58(11.4%)	86(13.1%)

Abbreviations: EM, Extensive metabolizer; IM, Intermediate metabolizer; PM, Poor metabolizer.

Table 5 Association of the CYP2C19 Metabolic Phenotypes with CI and CI Complicated with CAD Compared with CAD

Variables	CI				CI Complicated with CAD
	Univariate OR (95% CI)	P values	Multivariate OR (95% CI)	P values	Univariate OR (95% CI)	P values	Multivariate OR (95% CI)	P values
Age (≥65/<65)	0.879 (0.668–1.156)	0.356	0.830 (0.624–1.105)	0.201	2.070 (1.425–3.008)	<0.001	1.820 (1.236–2.680)	0.002
Gender (Male/Female)	0.937 (0.709–1.239)	0.649	1.030 (0.757–1.401)	0.853	1.078 (0.771–1.506)	0.661	1.401 (0.976–2.009)	0.067
History of smoking (Yes/No)	0.853 (0.628–1.159)	0.309	0.859 (0.608–1.214)	0.390	0.472 (0.311–0.718)	<0.001	0.524 (0.333–0.824)	0.005
History of alcohol consumption (Yes/No)	1.242 (0.626–2.465)	0.535	1.284 (0.628–2.624)	0.493	0.613 (0.224–1.682)	0.342	0.809 (0.283–2.314)	0.692
Hypertension (Yes/No)	1.948 (1.465–2.591)	<0.001	1.953 (1.459–2.612)	<0.001	1.910 (1.359–2.685)	<0.001	1.830 (1.288–2.602)	0.001
Diabetes (Yes/No)	0.927 (0.700–1.229)	0.600	0.838 (0.627–1.119)	0.230	1.266 (0.918–1.745)	0.151	1.148 (0.820–1.605)	0.422
CYP2C19 metabolic phenotypes
EM	1.000 (Reference)		1.000 (Reference)		1.000 (Reference)		1.000 (Reference)
IM	1.443 (1.092–1.908)	0.010	1.443 (1.086–1.918)	0.011	1.518 (1.092–2.111)	0.013	1.409 (1.004–1.979)	0.048
PM	1.476 (0.971–2.245)	0.069	1.427 (0.932–2.186)	0.102	1.377 (0.832–2.279)	0.213	1.314 (0.782–2.209)	0.302
IM or PM	1.450 (1.113–1.890)	0.006	1.440 (1.100–1.885)	0.008	1.488 (1.087–2.038)	0.013	1.389 (1.006–1.920)	0.046

Abbreviations: EM, Extensive metabolizer; IM, Intermediate metabolizer; PM, Poor metabolizer.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.