Role of CYP19A1 Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population

Figures & data

Table 1 The Basic Information of the Selected Variants Located in CYP19A1

SNP-ID	Gene	Chr: Position	Consequence	Allele	MAF		HWE p-value	HaploReg
					Case	Control
rs28757157	CYP19A1	15:51253204	Intron_variant	C/T	0.241	0.206	0.402	Motifs changed, Selected eQTL hits
rs3751592	CYP19A1	15:51314381	2KB_upstream_variant	C/T	0.137	0.118	0.851	DNAse, Motifs changed, Selected eQTL hits
rs3751591	CYP19A1	15:51314513	2KB_upstream_variant	G/A	0.143	0.143	0.202	DNAse, Motifs changed
rs59429575	CYP19A1	15:51314880	2KB_upstream_variant	C/T	0.190	0.156	0.370	DNAse, Proteins bound, Motifs changed

Notes: p-value was calculated from Person’s chi-square test.

Abbreviations: SNP, single nucleotide polymorphism; MAF, minor allele frequency; HWE, Hardy–Weinberg equilibrium; A, minor alleles; B, major alleles.

Table 2 The Association Between CYP19A1 Polymorphisms and Ischemic Stroke Risk (Overall Analysis)

SNP-ID	Model	Genotype	Frequency		With Adjustment
			Case	Control	OR (95% CI)	p-value
rs28757157	Allele	C	988	1034	1
		T	314	268	1.23 (1.02–1.48)	0.030
	Codominant	C/C	369	414	1
		C/T	250	206	1.42 (1.12–1.81)	0.004
		T/T	32	31	1.16 (0.69–1.96)	0.575
	Dominant	C/C	369	414	1
		C/T-T/T	282	237	1.39 (1.10–1.74)	0.005
	Recessive	C/C-C/T	619	620	1
		T/T	32	31	1.02 (0.61–1.71)	0.935
	Log-additive	–	–	–	1.26 (1.04–1.53)	0.018
rs3751592	Allele	T	1124	1149	1
		C	178	153	1.19 (0.94–1.50)	0.141
	Codominant	T/T	489	506	1
		C/T	146	137	1.14 (0.87–1.49)	0.359
		C/C	16	18	2.15 (0.89–5.19)	0.088
	Dominant	T/T	489	506	1
		C/T-C/C	162	145	1.19 (0.92–1.55)	0.192
	Recessive	C/T-T/T	635	643	1
		C/C	16	8	2.10 (0.87–5.05)	0.099
	Log-additive	–	–	–	1.22 (0.96–1.54)	0.102
rs3751591	Allele	A	1116	1113	1
		G	186	185	1.00 (0.80–1.25)	0.981
	Codominant	A/A	477	473	1
		G/A	162	167	0.98 (0.76–1.27)	0.879
		G/G	12	9	1.56 (0.64–3.80)	0.333
	Dominant	A/A	477	473	1
		G/G-G/A	174	176	1.01 (0.78–1.30)	0.952
	Recessive	G/A-A/A	639	640	1
		G/G	12	9	1.56 (0.64–3.81)	0.326
	Log-additive	–			1.04 (0.83–1.30)	0.756
rs59429575	Allele	C	1054	1099	1
		T	248	203	1.27 (1.04–1.56)	0.020
	Codominant	C/C	425	467	1
		C/T	204	165	1.47 (1.14–1.88)	0.003
		T/T	22	19	1.32 (0.70–2.49)	0.397
	Dominant	C/C	425	467	1
		T/T-C/T	226	184	1.45 (1.14–1.84)	0.003
	Recessive	C/T-C/C	629	632	1
		T/T	22	19	1.18 (0.63–2.22)	0.608
	Log-additive	–	–	–	1.34 (1.09–1.65)	0.006

Notes: p-value was calculated by logistic regression analysis with adjustments for age and gender. Bold values indicated that the p-value was statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Figure 1 The forest map showed the association between CYP19A1 polymorphisms and ischemic stroke risk (overall analysis).

Table 3 The Association Between CYP19A1 Polymorphisms and Ischemic Stroke Risk (Age and Gender Stratified Analysis)

SNP	Model	Genotype	>60		≤60		Female		Male
			OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
rs28757157	Allele	C	1		1		1		1
		T	1.34 (1.04–1.73)	0.023	1.15 (0.87–1.52)	0.315	1.42 (1.02–1.98)	0.038	1.15 (0.92–1.44)	0.224
	Codominant	C/C	1		1		1		1
		C/T	1.46 (1.04–2.06)	0.029	1.27 (0.88–1.84)	0.208	1.70 (1.11–2.62)	0.015	1.29 (0.97–1.72)	0.084
		T/T	1.33 (0.62–2.84)	0.467	1.04 (0.45–2.41)	0.925	1.20 (0.51–2.87)	0.675	1.14 (0.59–2.21)	0.703
	Dominant	C/C	1		1		1		1
		C/T-T/T	1.45 (1.04–2.00)	0.028	1.24 (0.87–1.78)	0.238	1.62 (1.08–2.43)	0.020	1.27 (0.96–1.68)	0.091
	Recessive	C/C-C/T	1		1		1		1
		T/T	1.16 (0.55–2.47)	0.691	0.95 (0.41–2.16)	0.896	1.01 (0.43–2.39)	0.977	1.03 (0.54–1.98)	0.928
	Log-additive	–	1.32 (1.00–1.74)	0.048	1.16 (0.86–1.56)	0.346	1.38 (0.99–1.92)	0.059	1.19 (0.94–1.51)	0.144
rs59429575	Allele	C	1		1		1		1
		T	1.28 (0.97–1.70)	0.082	1.34 (0.99–1.82)	0.057	1.17 (0.83–1.65)	0.382	1.33 (1.04–1.72)	0.025
	Codominant	C/C	1		1		1		1
		C/T	1.38 (0.97–1.98)	0.076	1.45 (0.99–2.14)	0.060	1.20 (0.78–1.84)	0.402	1.69 (1.24–2.32)	0.001
		T/T	1.96 (0.74–5.20)	0.176	1.14 (0.44–2.97)	0.788	1.88 (0.59–6.02)	0.289	1.23 (0.57–2.68)	0.596
	Dominant	C/C	1		1		1		1
		T/T-C/T	1.43 (1.01–2.03)	0.043	1.42 (0.97–2.06)	0.069	1.25 (0.83–1.89)	0.291	1.64 (1.21–2.21)	0.001
	Recessive	C/T-C/C	1		1		1		1
		T/T	1.78 (0.68–4.71)	0.242	1.02 (0.39–2.63)	0.973	1.78 (0.56–5.64)	0.331	1.06 (0.49–2.29)	0.878
	Log-additive	–	1.46 (1.04–2.06)	0.034	1.29 (0.94–1.77)	0.118	1.25 (0.87–1.80)	0.218	1.44 (1.11–1.87)	0.006

Notes: p-value was calculated by logistic regression analysis with adjustments for age and gender. Bold values indicated that the p-value was statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 4 The Association Between CYP19A1 Polymorphisms and Ischemic Stroke Risk (BMI Stratified Analysis)

SNP	Model	Genotype	≥24		<24
			OR (95% CI)	p-value	OR (95% CI)	p-value
rs28757157	Allele	C	1		1
		T	1.13 (0.81–1.56)	0.476	1.27 (1.02–1.60)	0.035
	Codominant	C/C	1		1
		C/T	1.36 (0.87–2.12)	0.176	1.45 (1.09–1.93)	0.012
		T/T	1.26 (0.54–2.95)	0.595	1.16 (0.59–2.29)	0.672
	Dominant	C/C	1		1
		C/T-T/T	1.34 (0.88–2.04)	0.169	1.41 (1.07–1.87)	0.015
	Recessive	C/C-C/T	1		1
		T/T	1.14 (0.49–2.63)	0.757	1.00 (0.51–1.96)	0.996
	Log-additive	–	1.23 (0.88–1.71)	0.225	1.29 (1.02–1.63)	0.037
rs59429575	Allele	C	1		1
		T	1.45 (1.02–2.07)	0.041	1.19 (0.93–1.53)	0.162
	Codominant	C/C	1		1
		C/T	1.87 (1.18–2.98)	0.008	1.33 (0.98–1.79)	0.067
		T/T	1.63 (0.58–4.61)	0.358	1.19 (0.52–2.71)	0.688
	Dominant	C/C	1		1
		T/T-C/T	1.84 (1.18–2.86)	0.007	1.31 (0.98–1.76)	0.067
	Recessive	C/T-C/C	1		1
		T/T	1.37 (0.49–3.85)	0.548	1.09 (0.48–2.48)	0.837
	Log-additive	–	1.59 (1.10–2.30)	0.014	1.24 (0.96–1.61)	0.096

Notes: p-value was calculated by logistic regression analysis with adjustments for age and gender. Bold values indicated that the p-value was statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 5 The Association Between CYP19A1 Polymorphisms and Ischemic Stroke Risk (Smoking and Drinking Stratified Analysis)

SNP	Model	Genotype	Smoking		No-Smoking		Drinking		No-Drinking
			OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
rs28757157	Allele	C	1		1		1		1
		T	1.15 (0.88–1.50)	0.293	1.31 (1.01–1.69)	0.043	1.36 (1.04–1.80)	0.026	1.13 (0.88–1.45)	0.345
	Codominant	C/C	1		1		1		1
		C/T	1.27 (0.90–1.79)	0.174	1.50 (1.07–2.10)	0.018	1.36 (0.60–3.08)	0.026	1.27 (0.91–1.76)	0.155
		T/T	1.25 (0.58–2.68)	0.568	1.11 (0.53–2.32)	0.783	1.20 (0.51–2.87)	0.463	1.03 (0.51–2.08)	0.934
	Dominant	C/C	1		1		1		1
		C/T-T/T	1.27 (0.91–1.76)	0.159	1.45 (1.05–1.99)	0.025	1.48 (1.05–2.08)	0.024	1.24 (0.90–1.69)	0.188
	Recessive	C/C-C/T	1		1		1		1
		T/T	1.15 (0.54–2.45)	0.718	0.95 (0.46–1.97)	0.896	1.19 (0.53–2.67)	0.679	0.94 (0.47–1.87)	0.860
	Log-additive	–	1.20 (0.91–1.58)	0.192	1.28 (0.98–1.68)	0.069	1.35 (1.01–1.80)	0.042	1.15 (0.88–1.48)	0.307
rs59429575	Allele	C	1		1		1		1
		T	1.48 (1.09–1.99)	0.011	1.13 (0.86–1.50)	0.384	1.48 (1.10–2.01)	0.010	1.12 (0.85–1.48)	0.410
	Codominant	C/C	1		1		1		1
		C/T	1.97 (1.35–2.88)	0.000	1.18 (0.84–1.67)	0.338	1.87 (1.27–2.74)	0.001	1.25 (0.89–1.75)	0.203
		T/T	1.71 (0.67–4.36)	0.264	0.95 (0.39–2.33)	0.910	1.89 (0.76–4.68)	0.171	0.91 (0.36–2.33)	0.848
	Dominant	C/C	1		1		1		1
		T/T-C/T	1.94 (1.35–2.79)	0.000	1.16 (0.83–1.61)	0.385	1.87 (1.30–2.70)	0.001	1.21 (0.87–1.68)	0.248
	Recessive	C/T-C/C	1		1		1		1
		T/T	1.42 (0.56–3.60)	0.460	0.90 (0.37–2.20)	0.819	1.59 (0.64–3.90)	0.316	0.85 (0.34–2.17)	0.737
	Log-additive	–	1.70 (1.24–2.33)	0.001	1.11 (0.83–1.47)	0.497	1.65 (1.21–2.26)	0.002	1.14 (0.86–1.53)	0.362

Notes: p-value was calculated by logistic regression analysis with adjustments for age and gender. Bold values indicated that the p-value was statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 6 The Association Between CYP19A1 Polymorphisms and Ischemic Stroke Risk (Clinical Information Analysis)

SNP	Model	Genotype	Hypertension vs Non-Hypertension		Coronary Heart Disease vs Non-Coronary Heart Disease		Diabetes vs Non-Diabetes
			OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
rs28757157	Allele	C	1		1		1
		T	0.86 (0.66–1.13)	0.291	1.03 (0.75–1.42)	0.834	0.66 (0.46–0.95)	0.025
	Codominant	C/C	1		1		1
		C/T	0.76 (0.54–1.08)	0.128	1.04 (0.68–1.58)	0.856	0.71 (0.46–1.09)	0.117
		T/T	1.01 (0.45–2.26)	0.984	1.31 (0.55–3.12)	0.541	0.27 (0.06–1.14)	0.075
	Dominant	C/C	1		1		1
		C/T-T/T	0.79 (0.56–1.10)	0.164	1.07 (0.72–1.60)	0.737	0.65 (0.42–0.99)	0.047
	Recessive	C/C-C/T	1		1		1
		T/T	1.13 (0.51–2.49)	0.770	1.29 (0.55–3.02)	0.557	0.30 (0.07–1.29)	0.106
	Log-additive	–	0.86 (0.65–1.14)	0.289	1.09 (0.78–1.51)	0.619	0.65 (0.44–0.94)	0.023
rs59429575	Allele	C	1		1		1
		T	0.99 (0.73–1.33)	0.930	1.08 (0.77–1.52)	0.662	0.81 (0.55–1.19)	0.289
	Codominant	C/C	1		1		1
		C/T	0.99 (0.68–1.42)	0.942	1.33 (0.87–2.04)	0.193	0.98 (0.63–1.53)	0.939
		T/T	0.89 (0.35–2.23)	0.796	0.94 (0.31–2.92)	0.921	0.23 (0.03–1.74)	0.154
	Dominant	C/C	1		1		1
		T/T-C/T	0.98 (0.69–1.39)	0.893	1.29 (0.85–1.95)	0.236	0.90 (0.58–1.39)	0.638
	Recessive	C/T-C/C	1		1		1
		T/T	0.89 (0.35–2.23)	0.802	0.86 (0.28–2.63)	0.790	0.23 (0.03–1.74)	0.155
	Log-additive	–	0.97 (0.71–1.32)	0.843	1.18 (0.83–1.68)	0.355	0.83 (0.57–1.23)	0.362

Notes: p-value was calculated by logistic regression analysis with adjustments for age and gender. Bold values indicated that the p-value was statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Figure 2 The circle graph showed that the interaction between rs28757157 and rs3751591 was synergistic, with the information gain value 0.35%.