SMAD4 rs10502913 is Significantly Associated with Chronic Obstructive Pulmonary Disease in a Chinese Han Population: A Case-Control Study

Figures & data

Table 1 Demographic and Selected Variables Among the COPD Cases and Control Subjects

Variables	COPD (N=376)		Control (284)		P
	N	%	N	%
Age (years)	69.74±10.40		62.00±10.91		<0.001
BMI	22.8±3.40		23.3±3.50		0.127
Smoking index	34.61±26.46		22.86±21.76		0.027
Smoking status					<0.001
Former	216	57.4	99	34.8
Current	121	32.2	113	39.8
Never	39	10.4	72	25.4
Pulmonary function
FVC observed (L)	2.61±0.89		3.58±0.81
FEV1 observed (L)	1.47±0.69		2.74±0.66
FEV1% predicted	54.28±22.68		89.29±16.07
FEV1/FVC (%)	54.29±11.09		76.53±4.60

Note: Data are presented as mean ±SD.

Abbreviations: N, number of subjects; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; COPD, chronic obstructive pulmonary disease; BMI, body mass index.

Table 2 Primary Information of Genotyped SNPs

Gene	SNP	Chromosomal Position	Base	MAF		HWE P
				Cases	Controls
SMAD4	rs10502913	chr18:51041901	G>A	0.286	0.327	0.592
IL-4	rs2070874	chr5:132674018	C>T	0.239	0.204	0.975
HSPA1L	rs2227956	chr6:31810495	G>A	0.159	0.188	0.851

Abbreviations: HWE, Hardy-Weinberg equilibrium; SNP, single nucleotide polymorphism; MAF, minor allele frequency.

Table 3 Distributions of Genotypes of Different Genes Their Associations with Risk of COPD

Variables	COPD		Controls		P	COR (95% CI)	AOR (95% CI)
	N	%	N	%
SMAD4 rs10502913	376		284
AA	23	6.1	35	12.3	0.022	1.00	1.00
AG	169	44.9	116	40.8	0.007	2.217 (1.245–3.947)	2.218 (1.204–4.151)
GG	184	48.9	133	46.8	0.011	2.105 (1.189–3.728)	2.235 (1.198–4.104)
A allele	215	28.6	186	32.7	0.104	1.00
G allele	537	71.4	382	67.3		1.216 (0.960–1.540)
IL-4 rs2070874	375		282
CC	20	5.3	11	3.9	0.321	1.00	1.00
CT	139	37.1	93	33.3	0.623	0.822 (0.376–1.795)	0.612 (0.264–1.419)
TT	216	57.6	178	63.1	0.298	0.667 (0.312–1.430)	0.549 (0.242–1.246)
C allele	179	23.9	115	20.4	0.134	1.00
T allele	571	76.1	449	79.6		0.817 (0.627–1.065)
HSPA1L rs2227956	375		284
AA	267	71.2	185	65.1	0.220	1.00	1.00
AG	97	25.9	91	32.0	0.082	0.739 (0.525–1.040)	0.790 (0.545–1.146)
GG	11	2.9	8	2.8	0.919	0.953 (0.376–2.414)	1.130 (0.417–3.058)
A allele	631	84.1	461	81.2	0.156	1.00
G allele	119	15.9	107	18.8		0.813 (0.610–1.083)

Note: P-values were calculated with Pearson’s χ² tests.

Abbreviations: COPD, chronic obstructive pulmonary disease; COR, crude odds ratio; AOR, adjusted odds ratio; CI, confidence interval; N, number of subjects.

Table 4 Analyses the Genotypes of SMAD4 rs10502913 Polymorphism and COPD Risk Stratified by Smoking Status and Age

Variables	Controls/Cases	Genotypes (Controls/Cases)						P^a	AOR (95% CI)	P^b	AOR (95% CI)
		AG		GG		AA
		N	%	N	%	N	%
Total	284/376	116/169	40.8/44.9	133/184	46.8/48.9	35/23	12.3/6.1	0.011	2.218 (1.204–4.151)	0.011	2.235 (1.198–4.104)
Smoking status
NO	72/39	36/14	50.0/35.9	23/22	31.9/56.4	13/3	18.1/7.7	0.587	1.498 (0.349–6.431)	0.063	3.949 (0.930–16.771)
YES	212/337	80/155	37.7/46.0	110/162	51.9/48.1	22/20	10.4/5.9	0.021	2.269 (1.132–4.548)	0.076	1.862 (0.936–3.703)
Smoking years
<30	151/105	70/41	46.4/39.0	54/57	35.8/54.3	27/7	17.9/6.7	0.135	2.125 (0.791–5.714)	0.009	3.751 (1.398–10.062)
≥30	133/271	46/128	34.6/47.2	75/127	56.4/46.9	12/16	9.0/5.9	0.077	2.131 (0.922–4.922)	0.382	1.442 (0.634–3.280)
Smoking index
≤20	173/124	79/45	45.7/36.3	68/71	39.3/57.3	26/8	15.0/6.4	0.124	2.078 (0.817–5.284)	0.003	4.003 (1.597–10.032)
>20	111/252	37/124	33.3/49.2	65/113	58.6/44.8	9/15	8.1/6.0	0.101	2.156 (0.860–5.402)	0.616	1.263 (0.508–3.124)
Age
<60	130/69	51/25	39.2/36.2	67/40	51.5/58.0	12/4	9.2/5.8	0.655	1.332 (0.378–4.693)	0.557	1.446 (0.422–4.951)
≥60	154/307	65/144	42.2/46.9	66/144	42.9/46.9	23/19	14.9/6.2	0.007	2.599 (1.304–5.176)	0.009	2.519 (1.266–5.015)

Notes: P-values were calculated by unconditional logistic regression adjusted for age, smoking status and smoking years. P^aStatistically significant difference between AA and AG; P^bStatistically significant difference between AA and GG; YES: including current smoking and former smoking.

Abbreviations: AOR, adjusted odds ratio; CI, confidence interval; N, number of subjects.

Table 5 Analyses the Genotypes of SMAD4 rs10502913 Polymorphism and COPD Risk Stratified by Severity

Variables	Cases	Genotypes (Controls/Cases)			P^a	AOR (95% CI)	P^b	AOR (95% CI)
		AG	GG	AA
		N	N	N
Total	376	116/169	133/184	35/23	0.011	2.218 (1.204–4.151)	0.011	2.235 (1.198–4.104)
Severity
GOLD I	66	116/26	133/37	35/3	0.103	2.921 (0.806–10.579)	0.046	3.628 (1.022–12.885)
GOLD II	139	116/60	133/71	35/8	0.540	2.370 (0.986–5.685)	0.049	2.394 (1.004–5.710)
GOLD III	108	116/54	133/47	35/7	0.047	2.532 (1.012–6.336)	0.178	1.886 (0.749–4.749)
GOLD IV	63	116/29	133/29	35/5	0.261	1.833 (0.637–5.276)	0.476	1.470 (0.509–4.243)

Notes: P-values were calculated by unconditional logistic regression adjusted for age, smoking status and smoking years. P^aStatistically significant difference between AA and AG; P^bStatistically significant difference between AA and GG.

Abbreviations: AOR, adjusted odds ratio; CI, confidence interval; N number of subjects.