GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study

Figures & data

Table 1 Basic Demographic Characteristics of the Study Population

Total Number of People	Case Group	Control Group	χ2/t	P-value
	312	314
Age (years)
≤60	52.63±5.92	47.70±7.86	83.410	<0.001*
>60	68.91±6.16	67.67±5.26
Gender
Male	169(54.2)	144(45.9)	4.320	0.038*
Female	143(45.8)	170(54.1)
Marital status
Unmarried	2(0.6)	6(1.9)
Married	281(90. 1)	278(88.5)	2.959	0.401
Divorced	26(8.3)	24(7.6)
Bereaved spouse BMI (kg/m^2)	3(1.0)	6(1.9)
<18.5	17.22±1.21	17.50±1.35
18.5–23.9	21.75±1.45	21.86±1.39	9.529	0.009*
≥24.0	26.47±2.11	26.82±2.19
Smoking
Yes	97(31.1)	53(16.9)	17.346	<0.001*
No	215(68.9)	261(83. 1)
Drinking
Yes	27(8.7)	39(12.4)	2.354	0. 125
No	285(91.3)	275(87.6)

Note: *Statistically significant parameters.

Abbreviation: BMI, Body mass index.

Table 2 Association of SNPs in GSTP1 and NLRP3 with COPD Susceptibility

Models	Genotype	Case Group (n=312)	Control Group (n=314)	P^a	Corrected OR (95% CI)^b	P^b	Akachi Information Guidelines (AIC)
		n (%)	n (%)
GSTP1
rs4147581C>G	CC	54(17.3)	119 (37.9)	<0.001*			737.397
	CG	128(41.0)	114 (36.3)		3.11 (1.961–4.935)	<0.001*
Additionality	GG	130 (41.7)	81(25.8)		2.065 (1.273–3.350)	0.003*
Dominant	CG+GG vs CC	258 (82.7)	195(62.1)	<0.001*	2.594 (1.718–3.916)	<0.001*	740.581
Implicit	GG vs CC+CG	130 (41.7)	81(25.8)	<0.001*	1.081 (0.724–1.615)	0.703	761.741
rs1695A>G	AA	223 (71.5)	225 (71.7)	0.999			746.732
	AG	63(20.1)	63(20.1)		2.495 (1.558–3.996)	<0.001*
Additionality	GG	26(8.3)	26(8.3)		1.583 (0.830–3.021)	0.163
Dominant	AG+GG vs AA	89(28.5)	89(28.3)	0.960	2.619 (1.428–3.294)	<0.001*	748.290
Implicit	GG vs AA+AG	26(8.3)	26(8.3)	0.981	1.243 (0.671–2.304)	0.489	761.409
NLRP3
rs3806265T>C	TT	220(70.5)	158(50.3)	<0.001*			741.553
	TC	82(26.3)	145 (46.2)		0.432 (0.296–0.630)	<0.001*
Additionality	CC	10(3.2)	11(3.5)		1.116 (0.433–2.875)	0.821
Dominant	TC+CCvs.TT	92(29.5)	156 (49.7)	<0.001*	2.132 (1.479–3.074)	<0.001*	745.150
Implicit	CC vs.TT+TC	10(3.2)	11(3.5)	0.836	1.568 (0.618–3.979)	0.344	761.003
rs10754558G>C	GG	226 (72.4)	234 (74.5)	0.833			761.692
	GC	78(25.0)	73(23.2)		0.939 (0.628–1.405)	0.760
Additionality	CC	8(2.6)	7(2.2)		1.184 (0.379–3.697)	0.771
Dominant	GC+CC vs.GG	86(27.6)	80(25.5)	0.554	0.959 (0.650–1.415)	0.832	761.841
Implicit	CC vs GG+GC	8(2.6)	7(2.2)	0.784	1.202 (0.387–3.736)	0.750	761.785

Notes: *Statistically significant parameters. ^aχ² test. ^bLogistic regression after correction for sex, age, BMI, and smoking.

Abbreviations: OR, dominance ratio; CI, confidence interval; AIC, red pool information criterion.

Table 3 Stratification Analysis and Interaction Analysis Between GSTP1 rs4147581C>G and COPD Susceptibility

Variables	Case Group (n=312)		Control Group (n=314)		GG+GCvs.CC	p Homo^b	CMH OR (95% CI)^c	PCMH ^c	P Inter^d
	CC	CG+GG	CC	CG+GG	OR (95% CI)^a
	n (%)	n (%)	n (%)	n (%)
Age
≤60	37(29.8)	87(70.2)	79(33.2)	159(66.8)	1.168 (0.730–1.869)	<0.001*	–	<0.001*	<0.001*
>60	17(9.0)	171 (91.0)	40(52.6)	36(47.4)	11.176 (5.709–21.879)		–
Gender
Male	3(1.8)	166 (98.2)	42(29.2)	102(70.8)	22.784 (6.883–75.418)	<0.001*	–	<0.001*	<0.001*
Female	51(35.7)	92 (64.3)	77(45.3)	93(54.7)	1.494 (0.946–2.357)		–
Marital status
Unmarried	1(50.0)	1(50.0)	2(33.3)	4(66.7)	0.500 (0.019–12.898)	0.429	2.950 (2.031–4.286)	<0.001*	0.217
Married	45(16.0)	236 (84.0)	106(38.1)	172(61.9)	3.232 (2.166–4.823)
Divorced	8(30.8)	18(69.2)	10(41.7)	14(58.3)	1.607 (0.502–5.141)
Bereaved spouse	1(11. 1)	8(88.9)	1(16.7)	5(83.3)	0.833 (0.583–1. 192)
BMI (kg/m)^2
<18.5	3(16.7)	15(83.3)	1(20.0)	4(80.0)	1.250 (0. 01–15.499)	0.767	2.862 (1.968–4.162)	<0.001*	0.916
18.5–23.9	24(15.4)	132(84.6)	53(36. 1)	94(63.9)	3.101 (1.789–5.375)
≥24.0	27(19.6)	111(80.4)	65(40. 1)	97(59.9)	2.755 (1.630–4.657)
Smoking status
Yes	2(2.1)	95 (97.9)	18(34.0)	35(66.0)	24.429 (5.389–110.737)	<0.001*	–	<0.001*	0.298
No	52(24.2)	163 (75.8)	101(38.7)	160(61.3)	1.979 (1.327–2.950)		–
Drinking							–
Yes	0(0.0)	27(100.0)	11(28.2)	28(71.8)	2.766 (1.887–4.056)	0.059	3.046 (2.090–4.439)	<0.001*	0.057
No	54(18.9)	231 (81.1)	108(39.3)	167(60.7)	0.718 (0.590–0.874)
Past medical history
Yes	25(16.4)	127 (83.6)	48(37.2)	81(62.8)	3.010 (1.723–5.260)	0.859	2.898 (1.997–4.205)	<0.001*	0.687
No	29(18.1)	131 (81.9)	71(38.4)	114(61.6)	2.813 (1.707–4.637)

Notes: *Statistically significant parameters. ^aAdjusted logistic regression model analysis for gender, age, BMI, smoking, etc. ^bBreslow-Day test of heteroscedasticity. ^cCochran-Mantel-Haenszel test. ^dMultiplicative interaction.

Abbreviations: OR, dominance ratio; CI, confidence interval; BMI, Body mass index.

Table 4 Stratified Analysis and Interaction Analysis Between NLRP3 rs380626 T>C and COPD Susceptibility

Variables	Case Group (n=312)		Control Group (n=314)		TC+CCvs.TT	p Homo^b	CMH OR (95% CI) ^c	PCMH ^c	P Inter^d
	TT	TC+CC	TT	TC+CC	OR (95% CI) ^a
	n (%)	n (%)	n (%)	n (%)
Age
≤60	86(69.4)	38(30.6)	110(46.2)	128(53.8)	2.633 (1.664–4.168)	0.106	2.088 (1.469–2.968)	<0.001*	0.123
>60	134(71.3)	54(28.7)	48(63.2)	28(36.8)	1.448 (0.824–2.542)
Gender
Male	140(82.8)	29(17.2)	85(59.0)	59(41.0)	3.351 (1.993–5.635)	0.050	2.268 (1.619–3.176)	<0.001*	0.850
Female	80(55.9)	63(44.1)	73(42.9)	97(57.1)	1.687 (1.077–2.642)
Marital status
Unmarried	1(50.0)	1(50.0)	5(83.3)	1(16.7)	0.200 (0.006–6.664)	0.021*	–	<0.001*	0.210
Married	205(73.0)	76(27.0)	136(48.9)	142(51.1)	2.816 (1.979–4.008)		–
Divorced	11(42.3)	15(57.7)	13(54.2)	11(45.8)	0.621 (0.203–1.898)		–
Bereaved spouse	3(100.0)	0(0.0)	4(66.7)	2(33.3)	0.667 (0.379–1.174)		–
BMI (kg/m)^2							–
< 18.5	12(66.7)	6(33.3)	1(20.0)	4(80.0)	8.000 (0.725–88.226)	0.540	2.432 (1.743–3.392)	<0.001*	0.992
18.5–23.9	109(69.9)	47(30. 1)	70(47.6)	77(52.4)	2.551 (1.593–4.085)
≥ 24.0	99(71.7)	39(28.3)	87(53.7)	75(46.3)	188 (1.351–3.545)
Smoking status
Yes	82(84.5)	15(15.5)	23(43.4)	30(56.6)	7.130 (3.291–15.451)	0.001*	–	<0.001*	0.006*
No	138(64.2)	77(35.8)	135(51.7)	126(48.3)	1.673 (1.156–2.421)		–
Drinking
Yes	19(70.4)	8 (29.6)	16(41.0)	23(59.0)	3.414 (1.202–9.696)	0.453	2.339 (1.683–3.251)	<0.001*	0.005*
No	201(70.5)	84(29.5)	142(51.6)	133(48.4)	2.241 (1.583–3.173)
Past medical history
Yes	111 (73.0)	41(27.0)	66 (51.2)	63 (48.8)	2.584 (1.571–4.250)	0.597	2.336 (1.680–3.247)	<0.001*	0.239
No	109 (68.1)	51(31.9)	92 (49.7)	93(50.3)	2.160 (1.391–3.355)

Notes: *Statistically significant parameters. ^aAdjusted logistic regression model analysis for gender, age, BMI, smoking, etc. ^bBreslow-Day heteroscedasticity test. ^cCochran-Mantel-Haenszel test. ^dMultiplicative interaction.

Abbreviations: OR, dominance ratio; CI, confidence interval; BMI, Body mass index.

Table 5 Analysis of the Relationship Between COPD Severity and SNPs

Genotyping	Mild (5)	Moderate (77)	Severe (24)	Very Severe (4)	χ2	P-value
rs4147581C>G
CC (14)	0	12	2	0	4.135	0.668
CG (42)	2	31	7	2
GG (54)	3	34	15	2
rs1695A>G
AA (86)	5	58	21	2	6.579	0.300
AG (7)	0	6	0	1
GG (17)	0	13	3	1
rs3806265T>C
TT (100)	3	72	21	4	9.804	0.224
TC (8)	2	4	2	0
CC (2)	0	1	1	0
rs10754558G>C
GG (14)	7	5	2	0	7.145	0.313
GC (42)	19	14	7	2
CC (54)	13	24	15	2