ACE gene polymorphism is associated with COPD and COPD with pulmonary hypertension: a meta-analysis

Figures & data

Table 1 Characteristics of case–control studies included in the meta-analysis

Study	Year	Country	Ethnicity	Cases/controls	Age	Method	Q score
					Case/control
COPD
Ahsan et al^Citation10	2004	India	Asian	27/66	NA	PCR-RFLP	7
Ayada et al^Citation20	2014	Turkey	Caucasian	47/64	NA	PCR-RFLP	6
Busquets et al^Citation11	2007	Spain	Caucasian	74/159	62±2/NA	PCR-RFLP	8
Gu et al^Citation22	2003	China	Asian	122/159	60.8/63.5	PCR-RFLP	5
Hopkinson et al^Citation13	2004	England	Caucasian	103/101	64.1±9.1/61.8±8.6	PCR-RFLP	7
Jiang and Zhang^Citation24	2002	China	Asian	60/30	34–80/35–78	PCR-RFLP	5
Kuzubova et al^Citation18	2013	Russia	Caucasian	63/95	60.4±1.0/57.3±1.7	PCR-RFLP	8
Mlak et al^Citation25	2016	Poland	Caucasian	206/165	63±9.4/64±10.6	PCR-RFLP	8
Pabst et al^Citation7	2009	Germany	Caucasian	152/158	62.8±11.1/63.9±18.4	PCR-RFLP	7
Simsek et al^Citation19	2013	Turkey	Caucasian	66/40	61.23±11.41/59.17±11.23	PCR-RFLP	7
Tkácová et al^Citation17	2005	Slovakia	Caucasian	66/118	65.4±2.5/63.5±1.2	PCR-RFLP	7
Ulasli et al^Citation16	2013	Turkey	Caucasian	80/49	65.1±7.60/54.6±7.8	PCR-RFLP	6
Xu^Citation21	2002	China	Asian	110/55	69.66±6.60/68.86±11.02	PCR-RFLP	5
Yildiz et al^Citation15	2003	Turkey	Caucasian	42/40	62±7/60±8	PCR-RFLP	7
Zhang et al^Citation23	2008	China	Asian	61/57	63.8±8.2/61.6±7.3	PCR-RFLP	6
PH
Jiang and Zhang^Citation24	2002	China	Asian	30/30	50–80/35–78	PCR-RFLP	5
Ulasli et al^Citation16	2013	Turkey	Caucasian	30/50	66.9±7.2/54.6±7.8	PCR-RFLP	6
Xu^Citation21	2002	China	Asian	57/53	70.02±8.21/68.86±11.02	PCR-RFLP	5
Yildiz et al^Citation15	2003	Turkey	Caucasian	24/14	62±4.8/60±8	PCR-RFLP	6

Abbreviations: PH, pulmonary hypertension; NA, not available; PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism.

Table 2 Distributions of ACE allele and genotypes in different studies’ susceptibility to COPD

Study	Language	Year	COPD					Control					HWE
			DD	ID	II	D	I	DD	ID	II	D	I
COPD
Ahsan et al^Citation10	English	2004	5	12	10	22	32	10	31	23	51	77	0.93
Ayada et al^Citation20	English	2014	13	26	8	52	42	28	28	8	84	44	0.81
Busquets et al^Citation11	English	2007	27	40	7	94	54	53	79	27	185	133	0.79
Gu et al^Citation22	Chinese	2003	57	37	28	151	93	25	85	49	135	183	0.24
Hopkinson et al^Citation13	English	2004	25	49	29	99	107	24	49	28	97	105	0.78
Jiang and Zhang^Citation24	Chinese	2002	24	20	16	68	52	5	10	15	20	40	0.17
Kuzubova et al^Citation18	English	2013	17	29	17	63	63	22	49	24	93	97	0.75
Mlak et al^Citation25	English	2016	60	99	47	219	199	51	73	41	175	155	0.15
Pabst et al^Citation7	English	2009	33	76	43	142	162	50	69	39	169	147	0.12
Simsek et al^Citation19	English	2013	31	20	15	82	50	13	19	8	45	35	0.83
Tkácová et al^Citation17	English	2005	20	31	15	71	61	31	68	19	130	106	0.07
Ulasli et al^Citation16	English	2013	47	17	16	111	49	33	10	6	76	22	0.003
Xu^Citation21	Chinese	2002	22	56	32	100	120	7	25	23	39	71	0.96
Yildiz et al^Citation15	English	2003	14	21	7	49	35	12	18	10	42	38	0.54
Zhang et al^Citation23	Chinese	2008	13	27	21	53	69	9	28	20	46	68	0.88
			COPD with PH						COPD without PH
PH
Jiang and Zhang^Citation24	Chinese	2002	13	8		9	34	26	11	12		7	34	26	NA
Ulasli et al^Citation16	English	2013	19	6		5	44	16	28	11		11	67	33	NA
Xu^Citation21	Chinese	2002	16	25		16	57	57	6	31		16	43	63	NA
Yildiz et al^Citation15	English	2003	7		17		NA	NA	4		10		NA	NA	NA

Abbreviations: ACE, angiotensin-converting enzyme; HWE, Hardy–Weinberg equilibrium; PH, pulmonary hypertension; NA, not available.

Figure 1 The flow diagram of included and excluded studies.

Table 3 Summary of total results and subgroup analysis from different comparative genetic models

Genetic models	COPD						COPD+PH
	Na	OR	95% CI	P-value	Models	I^2 (%)	Na	OR	95% CI	P-value	Models	I^2 (%)
DD+ID vs II
Overall	15^Citation7,Citation10,Citation11,Citation13,Citation15–Citation25	1.10	0.90–1.34	0.34	Fixed	17.3	3^Citation16,Citation21,Citation24	1.05	0.59–1.89	0.86	Fixed	0
Asians	5^Citation10,Citation21–Citation24	1.48	1.07–2.03	0.02	Fixed	0	2^Citation21,Citation24	0.95	0.49–1.86	0.89	Fixed	0
Caucasians	10^Citation7,Citation11,Citation13,Citation15–Citation20,Citation25	0.92	0.71–1.18	0.49	Fixed	0	1^Citation16	1.41	0.44–4.55	0.57	Fixed	0
DD vs DI+II
Overall	15^Citation7,Citation10,Citation11,Citation13,Citation15–Citation25	1.27	0.88–1.82	0.21	Random	69.6	4^Citation15,Citation16,Citation21,Citation24	1.64	0.97–2.78	0.07	Fixed	0
Asians	5^Citation10,Citation21–Citation24	2.36	1.32–4.22	0.004	Random	51.8	2^Citation21,Citation24	2.05	1.00–4.19	0.05	Fixed	21.0
Caucasians	10^Citation7,Citation11,Citation13,Citation15–Citation20,Citation25	0.93	0.74–1.16	0.52	Fixed	26.6	2^Citation15,Citation16	1.25	0.57–2.74	0.57	Fixed	0
DD vs II
Overall	15^Citation7,Citation10,Citation11,Citation13,Citation15–Citation25	1.28	0.86–1.90	0.22	Random	58.4	3^Citation16,Citation21,Citation24	1.60	0.80–3.18	0.19	Fixed	0
Asians	5^Citation10,Citation21–Citation24	2.68	1.76–4.08	0.000	Fixed	25.9	2^Citation21,Citation24	1.65	0.71–3.83	0.24	Fixed	31.6
Caucasians	10^Citation7,Citation11,Citation13,Citation15–Citation20,Citation25	0.89	0.66–1.20	0.44	Fixed	5.7	1^Citation16	1.49	0.45–4.99	0.52	Fixed	0
DI vs II
Overall	15^Citation7,Citation10,Citation11,Citation13,Citation15–Citation25	0.99	0.80–1.22	0.91	Fixed	0	3^Citation16,Citation21,Citation24	0.79	0.41–1.50	0.47	Fixed	0
Asians	5^Citation10,Citation21–Citation24	1.07	0.75–1.51	0.71	Fixed	0	2^Citation21,Citation24	0.71	0.34–1.46	0.35	Fixed	0
Caucasians	10^Citation7,Citation11,Citation13,Citation15–Citation20,Citation25	0.94	0.72–1.23	0.66	Fixed	0	1^Citation16	1.20	0.28–5.12	0.81	Fixed	0
D vs I
Overall	15^Citation7,Citation10,Citation11,Citation13,Citation15–Citation25	1.14	0.91–1.41	0.25	Random	66.2	3^Citation16,Citation21,Citation24	1.30	0.90–1.87	0.16	Fixed	0
Asians	5^Citation10,Citation21–Citation24	1.63	1.17–2.27	0.004	Random	54.0	2^Citation21,Citation24	1.28	0.83–1.96	0.26	Fixed	0
Caucasians	10^Citation7,Citation11,Citation13,Citation15–Citation20,Citation25	0.94	0.81–1.09	0.41	Fixed	18.9	1^Citation16	1.35	0.67–2.75	0.40	Fixed	0

Note:

a Number of case–control studies.

Abbreviations: PH, pulmonary hypertension; OR, odds ratio.

Figure 2 Overall results of association between ACE gene polymorphism and COPD risk (DD+DI vs II).

Abbreviations: ACE, angiotensin-converting enzyme; OR, odds ratio.

Figure 3 Sensitivity analysis for the association between the ACE polymorphism and COPD risk.

Abbreviation: ACE, angiotensin-converting enzyme.

Figure 4 Forest plot for the association between ACE and COPD risk in dominant genetic model (DD+DI vs II).

Abbreviations: ACE, angiotensin-converting enzyme; OR, odds ratio.

Figure 5 Forest plot for the association between ACE and COPD risk in recessive genetic model (DD vs DI+II).

Note: Weights are from random-effects analysis.

Abbreviations: ACE, angiotensin-converting enzyme; OR, odds ratio.

Figure 6 Forest plot for the association between ACE and COPD risk in codominant genetic model (DD vs II).

Abbreviations: ACE, angiotensin-converting enzyme; OR, odds ratio.

Figure 7 Forest plot for the association between ACE and COPD risk in allele genetic model (D vs I).

Note: Weights are from random-effects analysis.

Abbreviations: ACE, angiotensin-converting enzyme; OR, odds ratio.

Figure 8 Funnel plot to test publication bias of studies under the dominant model (DD+DI vs II).

Abbreviations: OR, odds ratio; s.e., standard error.

Figure 9 Forest plot for the association between ACE and PH risk under recessive genetic model (DD vs DI+II).

Abbreviations: ACE, angiotensin-converting enzyme; PH, pulmonary hypertension; OR, odds ratio.

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