Genetic Variants of CYP4F2 Associated with Ischemic Stroke Susceptibility in the Han Population from Southern China

Figures & data

Table 1 Characteristics of Patients with IS and Healthy Individuals

Characteristics		Case	Control	p
		n = 661	n = 661
Age (Years)	Mean ± SD	63.68 ± 0.39	63.31 ± 0.232	0.409 ^a
	> 60	421 (63.7%)	464 (70.2%)
	≤ 60	240 (36.3%)	197 (29.8%)
Gender	Male	440 (66.6%)	436 (66%)	0.816 ^b
	Female	221 (33.4%)	225 (34%)
BMI (kg/m^2)	Mean ± SD	22.86 ± 0.11	22.94 ± 0.12	0.607 ^a
	≥24	241 (36.5%)	226 (34.2%)
	< 24	420 (63.5%)	435 (65.8%)
Smoking	Yes	317 (48%)	317 (48%)	1.000 ^b
	No	344 (52%)	344 (52%)
Drinking	Yes	330 (49.9%)	322 (48.7%)	0.660 ^b
	No	331 (50.1%)	339 (51.3%)
IS complicated with hypertension	Yes	459 (69.4%)	–
	No	202 (30.6%)	–
IS complicated with CHD	Yes	131 (19.8%)	–
	No	530 (80.2%)	–
IS complicated with diabetes	Yes	112 (16.9%)	–
	No	549 (83.1%)	–

Notes: ^aRepresents the p value calculated by the t-test; ^bRepresents the p value calculated by the chi-square test.

Abbreviations: IS, Ischemic stroke; SD, standard deviation; CHD, coronary heart disease.

Table 2 The Basic Information and HWE About the Candidate SNPs of CYP4F2

SNP ID	Function	Chr: Position	Alleles (A/B)	MAF		AF				HWE (P value)
				Cases	Controls	CHB	CHS	AFR	EUR
rs2108622	Missense variant	19: 15,879,621	A/G	0.321	0.277	0.218	0.200	0.082	0.290	0.923
rs3093106	Synonymous variant	19: 15,897,447	A/T	0.116	0.113	0.083	0.067	0.320	0.177	0.175
rs3093105	Missense variant	19: 15,897,578	C/A	0.119	0.113	0.083	0.067	0.239	0.176	0.175

Note: HWE P value >0.05 indicates that the genotypes were in Hard-Weinberg Equilibrium.

Abbreviations: A, minor allele; B, wild-type allele; SNP, Single nucleotide polymorphisms; MAF, minor allele frequency; AF, allele frequency; CHB, Han Chinese in Beijing, China; CHS, Han Chinese in Shanghai, China; EUR, European; AFR, African; HWE, Hardy–Weinberg equilibrium.

Figure 1 Flow chart of candidate SNP screening (rs3093106 and rs3093105).

Table 3 Association Between Candidate SNPs in CYP4F2 and Susceptibility to IS

SNP ID	Model	Genotype	Control	Case	OR (95% CI)	p-value
rs2108622	Allele	G	956 (72.31%)	897 (67.85%)	1
		A	366 (27.69%)	425 (32.15%)	1.24 (1.05–1.46)	0.012
	Codominant	GG	346 (52.3%)	303 (45.8%)	1
		AA	264 (39.9%)	291 (44%)	1.49 (1.01–2.22)	0.047
		GA	51 (7.7%)	67 (10.1%)	1.26 (1.01–1.58)	0.046
	Dominant	GG	346 (52.3%)	303 (45.8%)	1
		GA-AA	315 (47.7%)	358 (54.2%)	1.30 (1.05–1.61)	0.018
	Recessive	GG-GA	610 (92.3%)	594 (89.9%)	1
		AA	51 (7.7%)	67 (10.1%)	1.34 (0.92–1.97)	0.130
	Overdominant	GG-AA	397 (60.1%)	370 (56%)	1
		GA	264 (39.9%)	291 (44%)	1.19 (0.95–1.48)	0.130
	Log-additive	–	–	–	1.24 (1.05–1.46)	0.012
rs3093106	Allele	T	1172 (88.65%)	1169 (88.43%)	1
		A	150 (11.35%)	153 (11.57%)	1.02 (0.81–1.3)	0.855
	Codominant	TT	523 (79.1%)	517 (78.2%)	1
		CC	126 (19.1%)	135 (20.4%)	0.75 (0.31–1.8)	0.523
		CT	12 (1.8%)	9 (1.4%)	1.08 (0.82–1.42)	0.574
	Dominant	TT	523 (79.1%)	517 (78.2%)	1
		CT-CC	138 (20.9%)	144 (21.8%)	1.05 (0.81–1.37)	0.700
	Recessive	TT-CT	649 (98.2%)	652 (98.6%)	1
		CC	12 (1.8%)	9 (1.4%)	0.74 (0.31–1.77)	0.500
	Overdominant	TT-CC	535 (80.9%)	526 (79.6%)	1
		CT	126 (19.1%)	135 (20.4%)	1.09 (0.83–1.43)	0.540
	Log-additive	–	–	–	1.02 (0.80–1.29)	0.880
rs3093105	Allele	A	1172 (88.65%)	1165 (8.12%)	1
		C	150 (11.35%)	157 (11.88%)	1.05 (0.83–1.34)	0.671
	Codominant	AA	523 (79.1%)	513 (77.6%)	1
		CC	126 (19.1%)	139 (21%)	0.76 (0.32–1.82)	0.534
		CA	12 (1.8%)	9 (1.4%)	1.12 (0.86–1.47)	0.399
	Dominant	AA	523 (79.1%)	513 (77.6%)	1
		CA-CC	138 (20.9%)	148 (22.4%)	1.09 (0.84–1.42)	0.510
	Recessive	AA-CA	649 (98.2%)	652 (98.6%)	1
		CC	12 (1.8%)	9 (1.4%)	0.74 (0.31–1.77)	0.500
	Overdominant	AA-CC	535 (80.9%)	522 (79%)	1
		CA	126 (19.1%)	139 (21%)	1.13 (0.86–1.48)	0.380
	Log-additive	–	–	–	1.05 (0.83–1.33)	0.690

Notes: “–” indicates log-additive model. “p-value <0.05” and bold text represent statistical significance.

Abbreviations: IS, Ischemic stroke; SNP, single nucleotide polymorphisms; OR, odds ratio; CI, confidence interval.

Figure 2 Forest map based on the positive results observed in stratified analysis.

Table 4 CYP4F2 SNP–SNP Interaction Models Analyzed by the MDR Method

Model	Training Bal. Acc	Testing Bal. Acc	OR (95% CI)	p-value	CVC
rs2108622	0.533	0.533	1.30 (1.05 −1.61)	0.018	10/10
rs2108622, rs3093105	0.537	0.531	1.35 (1.08–1.67)	0.007	9/10
rs2108622, rs3093106, rs3093105	0.537	0.531	1.35 (1.08–1.67)	0.007	10/10

Notes: p values were calculated using χ²-tests; “p-value <0.05” and bold text represent statistical significance.

Abbreviations: MDR, multifactor dimensionality reduction; Bal. Acc., balanced accuracy; CVC, cross-validation consistency; OR, odds ratio; 95% CI, 95% confidence interval.