Genetic Polymorphisms of CYP2C9/CYP2C19 in Chronic Obstructive Pulmonary Disease

Figures & data

Table 1. The basic information of cases and controls.

Variables	Case (n = 313)	Control (n = 508)	p
Age ^a	60.05 ± 6.48	71.80 ± 10.09	<0.001*
Sex ^b			0.003*
Male	238 (76.0%)	337 (66.3%)
Female	75 (24.0%)	171 (33.7%)
Smoking status ^b			0.082
Yes	149 (47.60%)	216 (42.5%)
No	164 (52.4%)	292 (57.5%)
BMI, kg/m^2 (mean ± SD) ^a	24.67 ± 4.62	24.35 ± 4.58	0.587
Lung function (mean ± SD) ^a
Respiratory rate, breaths/min	22.85 ± 3.65	15.78 ± 5.23	<0.001*
FEV1, predicted (%)	47.99 ± 8.45	93.19 ± 10.56	<0.001*
FVC, predicted (%)	68.94 ± 9.78	97.39 ± 8.69	<0.001*
FEV1/FVC	0.56 ± 0.05	0.79 ± 0.04	<0.001*

BMI: body mass index; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity.

^a Student’s t-test is used.

^b Pearson’s χ ² test is used.

* p < 0.05 indicates statistical significance.

Table 2. Basic information of candidate SNPs in this study.

SNP	Chr	Gene	Position	Allele A/B	p ^a -HWE	OR (95% CI)	p ^b
rs10509679	10	CYP2C9	9,49,48,469	A/G	1.000	0.89 (0.72–1.12)	0.321
rs1934967	10	CYP2C9	9,49,81,669	T/C	1.000	1.16 (0.90–1.50)	0.250
rs1934968	10	CYP2C9	9,49,82,060	A/G	1.000	0.98 (0.80–1.22)	0.884
rs9332220	10	CYP2C9	9,49,84,186	A/G	0.433	0.64 (0.43–0.94)	0.021*
rs111853758	10	CYP2C19	9,47,93,932	G/T	0.138	0.65 (0.45–0.96)	0.027*
rs4494250	10	CYP2C19	9,48,04,000	A/G	0.467	1.05 (0.81–1.35)	0.714
rs75665761	10	CYP2C19	9,48,06,855	A/G	0.709	1.31 (0.89–1.93)	0.176

SNP: single nucleotide polymorphisms; Chr: chromosome; HWE: Hardy–Weinberg equilibrium; OR: odds ratio; 95% CI: 95% confidential interval.

^a p values were calculated by exact test. p < 0.05 are excluded.

^b p values were calculated by two-sided χ ².

*p < 0.05 indicates statistical significance.

Table 3. Genotype frequencies of the SNPs and their associations with risk of COPD.

SNP	Gene	Model	Genotype	Case	Control	OR (95% CI)	p
rs111853758	CYP2C19	Genotype	TT	257	414	1
			TG	40	85	0.86 (0.52–1.42)	0.564
			GG	0	8	/	/
		Dominant	TT	257	414	1
			TG-GG	40	93	0.77 (0.47–1.26)	0.295
		Recessive	TT-TG	297	499	1
			GG	0	8	/	/
		Additive	–	–	–	0.71 (0.45–1.12)	0.145
rs4494250	CYP2C19	Genotype	GG	201	320	1
			AG	100	158	1.01 (0.69–1.48)	0.964
			AA	12	15	1.66 (0.62–4.42)	0.313
		Dominant	GG	201	320	1
			AG + AA	112	173	1.06 (0.73–1.54)	0.765
		Recessive	GG + AG	301	478	1
			AA	12	15	1.65 (0.62–4.38)	0.312
		Additive	–	–	–	1.10 (0.80–1.52)	0.558
rs75665761	CYP2C19	Genotype	GG	264	448	1
			AG	49	58	1.59 (0.97–2.63)	0.068
			AA	0	2	/	/
		Dominant	GG	264	448	1
			AG + AA	49	60	1.51 (0.92–2.48)	0.103
		Recessive	GG + AG	313	506	1
			AA	0	2	/	/
		Additive	–	–	–	1.40 (0.87–2.26)	0.170
rs10509679	CYP2C9	Genotype	GG	161	245	1
			AG	129	213	1.15 (0.77–1.71)	0.500
			AA	23	46	0.59 (0.31–1.09)	0.092
		Dominant	GG	161	245	1
			AG + AA	152	259	1.01 (0.69–1.47)	0.980
		Recessive	GG + AG	289	458	1
			AA	23	46	/	/
		Additive	–	–	–	1.40 (0.87–2.26)	0.170
rs1934967	CYP2C9	Genotype	CC	201	346	1
			CT	100	145	1.29 (0.87–1.90)	0.202
			TT	11	15	1.66 (0.60–4.60)	0.328
		Dominant	CC	201	346	1
			TC-TT	111	160	1.32 (0.91–1.92)	0.148
		Recessive	CC-TC	301	491	1
			TT	11	15	1.54 (0.56–4.23)	0.402
		Additive	–	–	–	1.29 (0.93–1.79)	0.127
rs9332220	CYP2C9	Genotype	GG	274	418	1
			AG	39	84	0.79 (0.48–1.30)	0.357
			AA	0	6	/	/
		Dominant	GG	274	418	1
			AG + AA	39	90	0.73 (0.45–1.20)	0.214
		Recessive	GG + AG	313	502	1
			AA	0	6	/	/
		Additive	–	–	–	0.70 (0.44–1.11)	0.128
rs1934968	CYP2C9	Genotype	GG	96	186	1
			AG	152	240	1.15 (0.77–1.71)	0.500
			AA	33	77	0.59 (0.31–1.09)	0.092
		Dominant	GG	96	186	1
			AG + AA	185	317	1.01 (0.69–1.47)	0.980
		Recessive	GG + AG	248	426	1
			AA	33	77	0.54 (0.30–0.96)	0.037*
		Additive	–	–	–	0.86 (0.65–1.14)	0.295

OR: odds ratio; 95% CI: 95% confidential interval.

p‐values were calculated by unconditional logistic regression analysis with adjustment for age and sex.

* p < 0.05 indicates statistical significance.

Table 4. The association between SNPs and COPD under gender stratification analysis.

SNP	Model	Allele/Genotype	Male				Female
			Case	Control	OR (95% CI)	p	Case	Control	OR (95% CI)	p
CYPC219
rs111853758	Allele	T	418	602	1		136	311	1
		G	30	70	0.62 (0.40–0.96)	0.032*	10	31	0.74 (0.35–1.55)	0.419
	Genotype	TT	194	270	1		63	144	1
		TG	30	62	0.78 (0.42–1.43)	0.420	10	23	1.10 (0.46–2.63)	0.830
		GG	0	4	/	/	0	4	/	/
	Dominant	TT	194	270	1		63	144	1
		TG-GG	30	66	0.72 (0.39–1.32)	0.290	10	27	0.90 (0.38–2.09)	0.799
	Recessive	TT-TG	224	332	1		73	167	1
		GG	0	4	/	/	0	4	/	/
	Additive	–	–	–	0.69 (0.39–1.22)	0.200	–	–	0.78 (0.37–1.64)	0.507
rs4494250	Allele	G	387	534	1		115	264	1
		A	89	118	1.04 (0.77-1.41)	0.797	35	70	1.15 (0.72–1.82)	0.558
	Genotype	GG	159	221	1		42	99	1
		AG	69	92	0.94 (0.57–1.55)	0.806	31	66	1.11 (0.60–2.04)	0.478
		AA	10	13	1.54 (0.49–4.84)	0.456	2	2	2.75 (0.31–24.44)	0.364
	Dominant	GG	159	221	1		42	99	1
		AG + AA	79	105	1.00 (0.62–1.60)	0.990	33	68	1.15 (0.63–2.11)	0.647
	Recessive	GG + AG	228	313	1		73	165	1
		AA	10	13	1.57 (0.51–4.88)	0.434	2	2	2.64 (0.30–23.10)	0.380
	Additive	–	–	–	1.05 (0.71–1.58)	0.796	–	–	1.20 (0.69–2.11)	0.517
rs75665761	Allele	G	437	633	1		140	321	1
		A	39	41	1.38 (0.87–2.17)	0.166	10	21	1.09 (0.50–2.38)	0.825
	Genotype	GG	199	298	1		65	150	1
		AG	39	37	1.98 (0.92–3.63)	0.063	10	21	/	/
		AA	0	2	/	/	0	0	/	/
	Dominant	GG	199	298	1		65	150	1
		AG + AA	39	39	1.76 (0.94–3.29)	0.075	10	21	1.14 (0.48–2.68)	0.772
	Recessive	GG + AG	238	335	1		75	171	1
		AA	0	2	/	/	0	0	/	/
	Additive	–	–	–	1.55 (0.86–2.79)	0.149	–	–	1.14 (0.48–2.68)	0.772
CYP2C9
rs10509679	Allele	G	340	465	1		111	238	1
		A	136	205	0.91 (0.70–1.17)	0.460	39	100	0.84 (0.54–1.29)	0.418
	Genotype	GG	121	163	1		40	82	1
		AG	98	139	0.98 (0.62–1.55)	0.918	31	74	1.07 (0.58–1.99)	0.826
		AA	19	33	1.00 (0.44–2.26)	0.995	4	13	0.81 (0.23–2.85)	0.741
	Dominant	GG	121	163	1		40	82	1
		AG + AA	117	172	0.98 (0.63–1.52)	0.927	35	87	1.03 (0.57–1.88)	0.918
	Recessive	GG + AG	219	302	1		71	156	1
		AA	19	33	1.01 (0.46–2.22)	0.983	4	13	0.78 (0.23–2.67)	0.697
	Additive	–	–	–	0.99 (0.70–1.40)	0.951	–	–	0.98 (0.61–1.59)	0.939
rs1934967	Allele	C	389	561	1		113	276	1
		T	85	111	1.10 (0.81–1.51)	0.531	37	64	1.41 (0.89–2.24)	0.141
	Genotype	CC	161	238	1		40	108	1
		CT	67	85	1.18 (0.72–1.95)	0.516	33	60	1.49 (0.80–2.74)	0.206
		TT	9	13	1.47 (0.44–4.91)	0.532	2	2	3.16 (0.36–27.86)	0.301
	Dominant	CC	161	238	1		40	108	1
		TC-TT	76	98	1.21 (0.75–1.96)	0.436	35	62	1.54 (0.84–2.81)	0.163
	Recessive	CC-TC	228	323	1		73	168	1
		TT	9	13	1.40 (0.42–4.65)	0.580	2	2	2.70 (0.31–23.46)	0.369
	Additive	–	–	–	1.19 (0.79–1.79)	0.396	–	–	1.54 (0.88–2.70)	0.128
rs9332220	Allele	G	447	607	1		140	313	1
		A	29	67	0.59 (0.37–0.92)	0.020*	10	29	0.77 (0.37–1.63)	0.493
	Genotype	GG	209	273	1		65	145	1
		AG	29	61	0.71 (0.39–1.31)	0.275	10	23	1.03 (0.43–2.44)	0.947
		AA	0	3	/	/	0	3	/	/
	Dominant	GG	209	273	1		65	145	1
		AG + AA	29	64	0.67 (0.37–1.23)	0.194	10	26	0.90 (0.39–2.11)	0.816
	Recessive	GG + AG	238	334	1		75	168	1
		AA	0	3	/	/	0	3	/	/
	Additive	–	–	–	0.65 (0.36–1.15)	0.139	–	–	0.82 (0.38–1.77)	0.611
rs1934968	Allele	G	258	408	1		86	204	1
		A	172	260	1.05 (0.82–1.34)	0.721	46	134	0.81 (0.54–1.24)	0.336
	Genotype	GG	73	124	1		23	62	1
		AG	112	160	1.06 (0.64–1.74)	0.831	40	80	1.33 (0.69–2.56)	0.402
		AA	30	50	0.71 (0.34–1.51)	0.378	3	27	0.26 (0.06–1.03)	0.055
	Dominant	GG	73	124	1		23	62	1
		AG + AA	142	210	0.97 (0.60–1.57)	0.914	43	107	1.05 (0.55–1.99)	0.890
	Recessive	GG + AG	185	284	1		63	142	1
		AA	30	50	0.69 (0.35–1.38)	0.297	3	27	0.22 (0.06–10.82)	0.325
	Additive	–	–	–	0.90 (0.63–1.27)	0.542	–	–	0.77 (0.48–1.23)	0.274

OR: odds ratio; 95% CI: 95% confidential interval.

p values were calculated by logistic regression adjusted by age.

* p < 0.05 indicates statistical significance.