Association of genetic polymorphisms with chronic obstructive pulmonary disease in the Hainan population: a case-control study

Figures & data

Table 1 General characteristics of the study population

Variables	Case N (%)	Control N (%)	P-value
Age (years)	71.7±10.4	48.6±13.3	P<0.001a
Sex			P=0.935b
Male	142 (71.0%)	286 (71.3%)
Female	58 (29.0%)	115 (28.7%)
Nationality			P=0.889b
Han	166 (83%)	311 (82.5%)
Li	34 (17%)	70 (17.5%)
Smoking status			P=0.889b
Smoking	97 (48.5%)	191 (47.6%)
Non-smoking	103 (51.5%)	210 (52.4%)
BMI, kg/m^2	20.03 (±3.06)	21.06 (±3.41)	P=0.054a
FEV1/FVC	0.62 (±0.06)	0.80 (±0.02)
Total	200	401

Notes:

a P-values were calculated by Student’s t-tests;

b P-values were calculated from two-sided chi-square tests.

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced volume capacity.

Table 2 Allele frequencies in cases and controls and odds ratio estimates for COPD

SNP ID	Gene (s)	Band	Position	Alleles	MAF		HWE P-value	ORs	95% CI	Allele P-value
				Aa/B	Case	Control
rs2301104	HIF1A	14q23.2	62165028	C/G	0.095	0.105	1.000	0.897	0.599–1.343	0.598
rs7143164	HIF1A	14q23.2	62166755	C/G	0.150	0.136	1.000	1.122	0.798–1.577	0.508
rs10129270	HIF1A	14q23.2	62181954	A/G	0.145	0.126	0.655	1.174	0.829–1.662	0.366
rs8005745	HIF1A	14q23.2	62185295	T/A	0.153	0.138	0.835	1.120	0.799–1.571	0.511
rs4899056	HIF1A	14q23.2	62189531	T/C	0.158	0.140	0.838	1.152	0.824–1.610	0.408
rs966824	HIF1A	14q23.2	62200518	T/C	0.115	0.125	0.368	0.910	0.627–1.319	0.617
rs10873142	HIF1A	14q23.2	62203462	C/T	0.418	0.348	0.000#	1.344	1.050–1.719	0.019*
rs2301112	HIF1A	14q23.2	62206173	C/A	0.015	0.021	1.000	0.703	0.275–1.798	0.460
rs2301113	HIF1A	14q23.2	62206548	C/A	0.287	0.282	0.319	1.026	0.783–1.342	0.854
rs4902080	HIF1A	14q23.2	62208005	T/C	0.113	0.118	0.809	0.957	0.656–1.397	0.821
rs13180	IREB2	15q25.1	78789488	T/C	0.485	0.504	0.616	0.928	0729–1.180	0.540
rs66728	CHRNA5	15q25.1	78863472	C/T	0.443	0.430	1.000	1.051	0.862–1.339	0.685

Notes:

a Minor allele;

* P-value ≤0.05 indicates statistical significance;

# site with HWE P≤0.05 is excluded.

Abbreviations: COPD, chronic obstructive pulmonary disease; HWE, Hardy–Weinberg equilibrium; MAF, minor allele frequency; ORs, odds ratios; CI, confidence interval; SNP, single nucleotide polymorphism; CHRNA5, cholinergic receptor, neuronal nicotinic, alpha polypeptide-5; HIF1A, hypoxia-inducible factor 1α; IREB2, iron-responsive element-binding protein 2 gene.

Table 3 Logistic regression analysis of the association between IREB2 rs13180 and COPD risk

SNP	Model	Genotype	Control	Case	ORa (95% CI)	P-value	AIC	BIC
rs13180	Co-dominant	C/C	99 (25.1%)	48 (25.5%)	1.00	0.082	425.7	451.9
		T/C	192 (48.7%)	93 (49.5%)	0.99 (0.55–1.78)
		T/T	103 (26.1%)	47 (25%)	0.52 (0.26–1.04)
	Dominant	C/C	99 (25.1%)	48 (25.5%)	1.00	0.43	428.1	449.9
		T/C-T/T	295 (74.9%)	140 (74.5%)	0.80 (0.46–1.39)
	Recessive	C/C-T/C	291 (73.9%)	141 (75%)	1.00	0.025*	423.7	445.6
		T/T	103 (26.1%)	47 (25%)	0.52 (0.29–0.93)
	Over-dominant	C/C-T/T	202 (51.3%)	95 (50.5%)	1.00	0.21	427.2	449
		T/C	192 (48.7%)	93 (49.5%)	1.36 (0.84–2.22)
	Log-additive	–	–	–	0.72 (0.51–1.02)	0.065	425.3	447.2

Note:

a Adjusted for sex, age, and smoking status.

* P-value ≤0.05 indicates statistical significance.

Abbreviations: AIC, Akaike’s Information Criterion; BIC, Bayesian Information Criterion; IREB2, iron-responsive element-binding protein 2 gene; COPD, chronic obstructive pulmonary disease; SNP, single nucleotide polymorphism; OR, odds ratio; CI, confidence interval.

Figure 1 Linkage disequilibrium of polymorphic sites in the HIF1A gene.

Notes: A standard color scheme is used to display LD with bright red for very strong LD (LOD =2, D′=1), white for no LD (LOD <2, D′<1), pink red (LOD =2, D′<1), and blue (LOD <2, D′=1) for intermediate LD.
Abbreviations: HIF1A, hypoxia-inducible factor 1α; LD, linkage disequilibrium; LOD, likelihood of odds.

Table S1 Haplotypes of HIF1A and their association with COPD risk

	Haplotype	Freq	ORa (95% CI)	P-valuea
Block	GGGACCA	0.6148	1.00	–
	GGGACCC	0.1409	0.93 (0.55–1.58)	0.79
	GCATTTC	0.0994	1.09 (0.62–1.93)	0.76
	CGGACCA	0.0977	0.74 (0.39–1.37)	0.34
	GCATTCC	0.0212	1.42 (0.46–4.44)	0.54
	*******b	0.0259	0.74 (0.21–2.68)	0.65
Total	GGGACCAAC	0.6162	1.00	–
	GGGACCACC	0.1221	1.06 (0.52–2.14)	0.88
	GCATTTACT	0.0997	1.28 (0.66–2.49)	0.46
	CGGACCAAC	0.0977	0.80 (0.39–1.63)	0.54
	GCATTCACC	0.0212	2.12 (0.55–8.19)	0.28
	GGGACCCCC	0.0175	0.53 (0.08–3.49)	0.51
	*********b	0.0256	0.92 (0.21–4.15)	0.92

Notes: P-value ≤0.05 indicates statistical significance;

a adjusted for sex, age, smoking status.

*******b is on behalf of the other arrangement of these single nucleotide polymorphisms.

Abbreviations: COPD, chronic obstructive pulmonary disease; Freq, frequency; HIF1A, hypoxia-inducible factor 1α; OR, odds ratio; CI, confidence interval.

Table S2 Allele frequencies in cases and controls and odds ratio estimates for COPD in Han population

SNP ID	Gene (s)	Band	Position	Alleles	MAF		HWE P-value	ORs	95% CI	Allele P-value
				Aa/B	Case	Control
rs2301104	HIF1A	14q23.2	62165028	C/G	0.103	0.108	1.000	0.953	0.619–1.468	0.8267
rs7143164	HIF1A	14q23.2	62166755	C/G	0.166	0.142	1.000	1.200	0.835–1.724	0.3242
rs10129270	HIF1A	14q23.2	62181954	A/G	0.160	0.130	0.626	1.268	0.875–1.837	0.2091
rs8005745	HIF1A	14q23.2	62185295	T/A	0.169	0.145	1.000	1.196	0.835–1.714	0.3283
rs4899056	HIF1A	14q23.2	62189531	T/C	0.171	0.146	0.826	1.207	0.844–1.726	0.3011
rs966824	HIF1A	14q23.2	62200518	T/C	0.132	0.142	0.503	0.920	0.626–1.352	0.6709
rs10873142	HIF1A	14q23.2	62203462	C/T	0.431	0.369	0.000#	1.296	0.991–1.695	0.0580
rs2301112	HIF1A	14q23.2	62206173	C/A	0.018	0.024	1.000	0.743	0.288–1.917	0.5377
rs2301113	HIF1A	14q23.2	62206548	C/A	0.299	0.292	0.893	1.036	0.774–1.388	0.8102
rs4902080	HIF1A	14q23.2	62208005	T/C	0.129	0.133	1.000	0.967	0.654–1.430	0.8670
rs13180	IREB2	15q25.1	78789488	T/C	0.464	0.489	0.912	0.903	0.693–1.176	0.4482
rs66728	CHRNA5	15q25.1	78863472	C/T	0.446	0.447	0.658	0.995	0.763–1.297	0.9679

Notes:

a Minor allele;

# site with HWE P-value ≤0.05 is excluded.

Abbreviations: HWE, Hardy–Weinberg equilibrium; MAF, minor allele frequency; ORs, odds ratios; CI, confidence interval; SNP, single nucleotide polymorphism; COPD, chronic obstructive pulmonary disease; CHRNA5, cholinergic receptor, neuronal nicotinic, alpha polypeptide-5; HIF1A, hypoxia-inducible factor 1α; IREB2, iron-responsive element-binding protein 2 gene.