Variants in multiple genes polymorphism association analysis of COPD in the Chinese Li population

Figures & data

Table 1 Characteristics of study cases and controls

Characteristic	Case (N=234)	Control (N=240)	P-value
Sex, no (%)			0.617a
Male	142 (60.7)	151 (62.9)
Female	92 (39.3)	89 (37.1)
Smoking status, no (%)			0.162b
Nonsmoking	141 (60.3)	160 (66.7)
Smoking	90 (38.5)	78 (32.5)
Missing	3 (1.3)	2 (0.8)
Mean age ± SD	67.52±9.19	62.09±11.44	<0.001b

Notes: P<0.05 indicates statistical significance;

a for Pearson’s χ² test;

b for Welch’s t-test.

Abbreviation: SD, standard deviation.

Figure 1 The flow diagram of COPD subjects selected in this study.

Note: All subjects were Chinese Li minority population.
Abbreviations: BD, bronchodilator; FEV₁/FVC, forced expiratory volume in 1 second/forced vital capacity; COPD, chronic obstructive pulmonary disease.

Table 2 Information on the 16 SNPs in this study

SNPs	Chr	Position	Gene	A/B	HWE-P	OR	95% CI	Allele, P-valuea	P-valueb
rs7671167	4q22.1	89883979	FAM13A	T/C	0.502	1.19	0.92–1.54	0.187	1
rs950063	4q28.1	126431919	MIR2054	C/T	0.057	0.92	0.68–1.24	0.586	1
rs17050782	4q31.1	140423134	SETD7	G/A	0.070	1.40	1.07–1.83	0.014c	0.224
rs10007052	4q31.21	142005573	RNF150	C/A	0.248	0.75	0.52–1.08	0.120	1
rs1828591	4q31.21	145480780	HHIP	G/A	0.444	1.03	0.78–1.35	0.862	1
rs13118928	4q31.21	145486389	HHIP	G/A	0.277	1.05	0.79–1.38	0.743	1
rs13141641	4q31.21	145506456	HHIP	C/T	0.375	1.04	0.79–1.36	0.788	1
rs25648	6p21.1	43738977	VEGFA	T/C	0.568	1.63	0.63–4.23	0.521	1
rs833068	6p21.1	43742527	VEGFA	A/G	1	0.83	0.47–1.46	0.213	1
rs833070	6p21.1	43742626	VEGFA	A/G	0.145	0.84	0.63–1.11	0.884	1
rs3024994	6p21.1	43743507	VEGFA	T/C	0.481	1.02	0.77–1.36	0.113	1
rs3024997	6p21.1	43745107	VEGFA	A/G	0.880	0.75	0.52–1.08	0.208	1
rs3025000	6p21.1	43746169	VEGFA	T/C	1	0.84	0.63–1.11	0.210	1
rs3025030	6p21.1	43750587	VEGFA	C/G	0.593	0.84	0.63–1.11	0.272	1
rs3025033	6p21.1	43751075	VEGFA	G/A	0.592	1.22	0.86–1.73	0.248	1
rs10434	6p21.1	43753212	VEGFA	A/G	0.122	1.23	0.85–1.75	0.867	1

Notes:

a P-value was calculated using two-sided χ² tests;

b P-value was adjusted by Bonferroni correction;

c P<0.05 indicates statistical significance.

Abbreviations: Chr, chromosomes; A/B, minor/major allele; HWE, Hardy–Weinberg equilibrium; OR, odds ratio; CI, confidence interval; SNP, single nucleotide polymorphism.

Table 3 Association of rs17050782 with COPD in cases and controls

Model	Genotype	Controla	Casea	OR (95% CI)	P-value	AIC	BIC
Codominant	A/A	104 (44.1%)	88 (37.9%)	1	0.007b	644.9	657.3
	A/G	115 (48.7%)	106 (45.7%)	1.09 (0.74–1.61)
	G/G	17 (7.2%)	38 (16.4%)	2.64 (1.40–5.00)
Dominant	A/A	104 (44.1%)	88 (37.9%)	1	0.18	650.9	659.2
	A/G-G/G	132 (55.9%)	144 (62.1%)	1.29 (0.89–1.87)
Recessive	A/A-A/G	219 (92.8%)	194 (83.6%)	1	0.002b	643	651.3
	G/G	17 (7.2%)	38 (16.4%)	2.52 (1.38–4.61)
Overdominant	A/A-G/G	121 (51.3%)	126 (54.3%)	1	0.51	652.3	660.6
	A/G	115 (48.7%)	106 (45.7%)	0.89 (0.62–1.27)
Log-additive	–	–	–	1.42 (1.08–1.87)	0.012b	646.5	654.8

Notes:

a n=468, crude analysis;

b P<0.05 indicates statistical significance.

Abbreviations: COPD, chronic obstructive pulmonary disease; OR, odds ratio; CI, confidence interval; AIC, Akaike’s information criterion; BIC, Bayesian information criterion.

Table 4 Association of rs7671167 and rs17050782 with COPD in cases and controls

SNP	Model	Genotype	Controla	Casea	OR (95% CI)	P-value
		C/C	87 (36.5%)	68 (29.4%)	1
	Codominant	T/C	110 (46.2%)	120 (52%)	1.58 (1.02–2.43)	0.088
		T/T	41 (17.2%)	43 (18.6%)	1.59 (0.91–2.79)
	Dominant	C/C	87 (36.5%)	68 (29.4%)	1	0.028b
		T/C-T/T	151 (63.5%)	163 (70.6%)	1.58 (1.05–2.38)
rs7671167
		C/C-T/C	197 (82.8%)	188 (81.4%)	1
	Recessive					0.45
		T/T	41 (17.2%)	43 (18.6%)	1.21 (0.74–1.98)
		C/C-T/T	128 (53.8%)	111 (48%)	1
	Overdominant					0.14
		T/C	110 (46.2%)	120 (52%)	1.33 (0.91–1.95)
	Log-additive	–	–	–	1.30 (0.99–1.72)	0.057
	Co-dominant	A/G	114 (48.7%)	106 (46.3%)	1.09 (0.72–1.64)	0.026b
		G/G	17 (7.3%)	37 (16.2%)	2.41 (1.24–4.69)
	Dominant	A/A	103 (44%)	86 (37.5%)	1	0.23
rs17050782		A/G-G/G	131 (56%)	143 (62.5%)	1.27 (0.86–1.87)
	Recessive	A/A-A/G	217 (92.7%)	192 (83.8%)	1	0.008b
		G/G	17 (7.3%)	37 (16.2%)	2.30 (1.22–4.31)
	Overdominant	A/A-G/G	120 (51.3%)	123 (53.7%)	1	0.6
		A/G	114 (48.7%)	106 (46.3%)	0.90 (0.61–1.32)
	Log-additive	—	—	—	1.38 (1.03–1.85)	0.03b

Notes:

a n=469, adjusted for sex, age, and smoking status;

b P<0.05 indicates statistical significance.

Abbreviations: COPD, chronic obstructive pulmonary disease; OR, odds ratio; CI, confidence interval; SNP, single nucleotide polymorphism.

Table 5 Five SNPs in VEGFA haplotypes and risk of COPD adjusted for sex, age, and smoking status

rs833068	rs833070	rs3024994	rs3024997	rs3025000	Frequency	OR (95% CI)	P-value
A	G	C	A	T	0.29	1	–
G	A	C	G	C	0.28	1.11 (0.78–1.59)	0.57
G	G	C	G	C	0.28	1.48 (1.02–2.12)	0.037a
G	G	T	G	C	0.15	0.88 (0.57–1.37)	0.58

Note:

a P<0.05 indicates statistical significance.

Abbreviations: COPD, chronic obstructive pulmonary disease; OR, odds ratio; CI, confidence interval; SNP, single nucleotide polymorphism.

Figure 2 Linkage disequilibrium (LD) plots containing three single nucleotide polymorphisms (SNPs) from the 4q21.1 to 4q31.21.

Notes: LD analysis of the HHIP in Chinese Li controls. LD is indicated using standard color schemes with bright red signifying very strong LD (LOD ≥2, D′=1).

Abbreviation: LOD, likelihood of odds.

Figure 3 Linkage disequilibrium (LD) plots containing nine SNPs from the VEGFA.

Notes: LD analysis of VEGFA in Chinese Li controls. LD is indicated using standard color schemes with bright red signifying very strong LD (LOD ≥2, D′=1), pink red signifying relatively weak LD (LOD ≥2, D′,1).
Abbreviations: LOD, likelihood of odds; SNP, single nucleotide polymorphism.