EGLN2 and RNF150 genetic variants are associated with chronic obstructive pulmonary disease risk in the Chinese population

Figures & data

Table 1 Characteristics of COPD patients and control participants

	Cases (n=200)		Controls (n=401)		P-value from χ^2 test
	N	%	N	%
Sex
Female	58	29.0	115	28.7	0.935
Male	142	71.0	286	71.3
Age (years)
Mean	71.70		48.58		<0.001
Nationality
Han Chinese	166	83.0	331	82.5	0.889
Li Chinese	34	17.0	70	17.5
Smoking status
Nonsmoker	103	51.5	210	52.4	0.889
Smoker	97	48.5	191	47.6
Number of smokers
1–10 cigarettes a day	14	7.0	39	9.7	No data
20+ cigarettes a day	26	13.0	20	5.0
30+ cigarettes a day	53	26.5	78	19.5
Clinical stages
Stage I	80	40.0
Stage II	84	42.0
Stage III	26	13.0
Stage IV	10	5.0

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 2 Basic information on candidate tSNPs and their association with COPD risk in this study

SNP ID	Gene name	Chromosome	Base change	MAF (case)	MAF (control)	P-HWE	OR (95% CI)	P^a	P^b
rs1124480	WNT7A	3p25.1	C/T	0.228	0.239	0.782	0.94 (0.71–1.25)	0.667	0.665
rs7671167	FAM13A	4q22.1	T/C	0.475	0.481	0.318	0.98 (0.77–1.24)	0.837	0.840
rs10007052	RNF150	4q31.21	C/A	0.235	0.176	0.599	1.43 (1.06–1.95)	0.020*	0.021*
rs1828591	HHIP	4q31.21	G/A	0.286	0.298	0.146	0.95 (0.72–1.23)	0.681	0.691
rs13118928	HHIP	4q31.21	G/A	0.281	0.288	0.222	0.97 (0.74–1.27)	0.821	0.825
rs13141641	HHIP	4q31.21	C/T	0.290	0.287	0.221	1.01 (0.78–1.32)	0.913	0.915
rs13181561	TMEM173	5q31.2	A/G	0.327	0.383	0.833	0.78 (0.61–1.01)	0.057	0.062
rs3851050	PLAC9	10q22.3	C/T	0.315	0.291	0.276	1.12 (0.87–1.46)	0.382	0.373
rs954820	JAKMIP3	10q26.3	G/A	0.255	0.248	1.000	1.04 (0.79–1.37)	0.796	0.792
rs7937	EGLN2	19q13.2	C/T	0.413	0.364	0.829	1.23 (0.96–1.57)	0.101	0.103
rs3733829	EGLN2	19q13.2	C/T	0.354	0.407	0.680	0.80 (0.62–1.02)	0.077	0.078
rs8102683	CYP2A6	19q13.2	T/C	0.237	0.232	0.0000478	1.03 (0.77–1.37)	0.836	0.849
rs7260329	CYP2B6	19q13.2	G/A	0.305	0.287	4.397×10^−96	1.09 (0.84–1.42)	0.513	0.642
rs2823743	C21orf34	21q21.1	C/T	0.510	0.476	0.764	1.14 (0.90–1.45)	0.271	0.266

Notes:

* P<0.05 indicates statistical significance. P^a: P-values were calculated from chi-square tests or Fisher’s exact tests; P^b: P-values were calculated from Cochran-armitage trend test

Abbreviations: 95% CI, 95% confidence interval; COPD, chronic obstructive pulmonary disease; HWE, Hardy-Weinberg equilibrium; MAF, minor allele frequency; Or, odds ratio; SNP, single-nucleotide polymorphisms; tSNPs, tag SNPs.

Table 3 Association between rs10007052 genotypes and COPD risk under different genotypic models

Model	Genotype	Control	Case	Without adjustment		With adjustment
				P^a	OR (95% CI)	P^b	OR (95% CI)
Codominant	A/A	257 (68.2%)	106 (57.9%)	0.060	1.00	0.082	1.00
	C/A	107 (28.4%)	68 (37.2%)		1.54 (1.05–2.25)		1.63 (0.95–2.79)
	C/C	13 (3.5%)	9 (4.9%)		1.68 (0.70–4.04)		3.16 (0.73–13.66)
Dominant	A/A	257 (68.2%)	106 (57.9%)	0.018*	1.00	0.039*	1.00
	C/A-C/C	120 (31.8%)	77 (42.1%)		1.56 (1.08–2.24)		1.73 (1.03–2.90)
Recessive	A/A-C/A	364 (96.5%)	174 (95.1%)	0.410	1.00	0.180	1.00
	C/C	13 (3.5%)	9 (4.9%)		1.45 (0.61–3.45)		2.71 (0.64–11.53)
Over-dominant	A/A-C/C	270 (71.6%)	115 (62.8%)	0.037*	1.00	0.100	1.00
	C/A	107 (28.4%)	68 (37.2%)		1.49 (1.03–2.17)		1.55 (0.91–2.64)
Log-additive	–	–	–	0.022*	1.43 (1.05–1.95)	0.026*	1.68 (1.06–2.65)

Notes:

* P<0.05 indicates statistical significance. P^a: P-values were calculated from two-sided chi-square tests or Fisher’s exact tests for either genotype distribution. P^b: P-values were calculated by unconditional logistic regression adjusted for age, sex, and smoking.

Abbreviations: 95% CI, 95% confidence interval; COPD, chronic obstructive pulmonary disease; OR, odds ratio.

Table 4 Association between rs3733829 genotypes and COPD risk under different genotypic models

Model	Genotype	Control	Case	Without adjustment		With adjustment
				P^a	OR (95% CI)	P^b	OR (95% CI)
Codominant	T/T	138 (34.6%)	86 (43.2%)	0.120	1.00	0.059	1.00
	C/T	197 (49.4%)	85 (42.7%)		0.69 (0.48–1.00)		0.54 (0.32–0.93)
	C/C	64 (16%)	28 (14.1%)		0.70 (0.42–1.18)		0.55 (0.26–1.16)
Dominant	T/T	138 (34.6%)	86 (43.2%)	0.041*	1.00	0.018*	1.00
	C/T-C/C	261 (65.4%)	113 (56.8%)		0.69 (0.49–0.98)		0.55 (0.33–0.90)
Recessive	T/T-C/T	335 (84%)	171 (85.9%)	0.530	1.00	0.430	1.00
	C/C	64 (16%)	28 (14.1%)		0.86 (0.53–1.39)		0.76 (0.38–1.52)
Over-dominant	T/T-C/C	202 (50.6%)	114 (57.3%)	0.120	1.00	0.077	1.00
	C/T	197 (49.4%)	85 (42.7%)		0.76 (0.54–1.08)		0.64 (0.39–1.05)
Log-additive	–	–	–	0.077	0.80 (0.62–1.03)	0.037*	0.68 (0.48–0.98)

Notes:

* P<0.05 indicates statistical significance. P^a: P-values were calculated from two-sided chi-square tests or Fisher’s exact tests for either genotype distribution. P^b: P-values were calculated by unconditional logistic regression adjusted for age, sex, and smoking.

Abbreviations: 95% CI, 95% confidence interval; COPD, chronic obstructive pulmonary disease; OR, odds ratio.

Table 5 EGLN2 haplotype frequencies and their associations with COPD risk

Block	Haplotype	Frequency	OR (95% CI)	P^a	Frequency	OR (95% CI)	P^b
1	TC	0.3876	1.00	–	0.3883	1.00	–
2	CT	0.3772	1.31 (1.00–1.73)	0.055	0.3793	1.55 (1.05–2.31)	0.029*
3	TT	0.2331	1.15 (0.84–1.57)	0.39	0.23	1.30 (0.83–2.05)	0.26

Notes: P^a: P-values were calculated from two-sided chi-square tests or Fisher’s exact tests for either genotype distribution. P^b: P-values were calculated by unconditional logistic regression adjusted for age, sex, and smoking.

* P<0.05 indicates statistical significance.

Abbreviations: 95% CI, 95% confidence interval; COPD, chronic obstructive pulmonary disease; OR, odds ratio.

Figure 1 haplotype block map for the HHIP tSNPs genotyped in this study.

Notes: Block 1 includes rs1828591, rs13141641, and rs13118928; the linkage disequilibrium between two SNPs is indicated by standardized D′ (red boxes).
Abbreviations: SNP, single-nucleotide polymorphism; tSNPs, tag SNPs.