Association of the matrix metalloproteinase-3 polymorphisms rs679620 and rs3025058 with ischemic stroke risk: a meta-analysis

Figures & data

Figure 1 Flowchart depicting literature search and study selection.

Abbreviation: CNKI, China National Knowledge Infrastructure.

Table 1 Characteristics of individual studies included in the meta-analysis

Journal	First author	Year	Country	Ethnicity	Cases/controls	Cases		Controls		Stroke diagnosis	Source of controls	NOS	Genotyping
						Age	Male %	Age	Male %
(A) Case–control studies assessing the MMP-3 rs679620 polymorphism and ischemic stroke risk
Journal of Interferon & Cytokine Research	Kim et al^Citation18	2012	Korea	Asian	104/267	63.3±11.7	55.2	62.7±9.4	50.2	CT/MRI	Hospital- based	7	DNA sequencing
Chinese Journal of Medical Genetics	Ma et al^Citation19	2013	China	Asian	278/175	67.0±11.0 (LAA) 65.7±12.2 (SAO)	59.5 55.8	66.1±11.3	53.1	CT/MRI	Hospital-based	7	PCR
(B) Case–control studies assessing the MMP-3 rs3025058 polymorphism and ischemic stroke risk
Stroke	Ghilardi et al^Citation16	2002	Italy	Caucasian	41/133	68±7	NA	64±7	NA	CT	Hospital-based	6	DNA sequencing
Stroke	Flex et al^Citation17	2004	Italy	Caucasian	237/223	76.2±9.4	55.7	76.1±6.8	48.0	CT/MRI	Hospital-based	8	NA
Chinese Journal of Medical Genetics	Ma et al^Citation19	2013	China	Asian	270/170	67.0±11.0 (LAA) 65.7±12.2 (SAO)	59.5 55.8	66.1±11.3	53.1	CT/MRI	Hospital-based	7	PCR
International Journal of Clinical and Experimental Pathology	Hao et al^Citation20	2015	China	Asian	317/317	62.1±10.3	56.8	62.5±9.9	56.8	CT/MRI	Hospital-based	7	PCR-RFLP
Genetics and Molecular Research	Zhao et al^Citation21	2016	China	Asian	335/336	63.7±9.4	57.9	64.5±9.2	57.9	CT/MRI	Hospital-based	7	PCR-RFLP
Journal of Stroke and Cerebrovascular Diseases	Huang et al^Citation22	2017	China	Asian	640/637	64.6±12.4	59.4	64.9±12.4	59.8	CT/MRI	Hospital-based	7	PCR-RFLP

Abbreviations: CT, computed tomography; HWE, Hardy–Weinberg equilibrium; LAA, large artery atherosclerotic; MMP-3, matrix metalloproteinase-3; MRI, magnetic resonance imaging; NA, not available; NOS, Newcastle–Ottawa Scale; PCR, polymerase chain reaction; PCR-RFLP, PCR-restriction fragment length polymorphism; SAO, small artery occlusion.

Table 2 Genotypic and allelic distributions of the MMP-3 polymorphism in ischemic stroke patients and controls

Polymorphism	Stroke patients						Controls
	Total	GG (%)	GA (%)	AA (%)	G allele (%)	A allele (%)	Total	GG (%)	GA (%)	AA (%)	G allele (%)	A allele (%)
rs679620
Kim et al^Citation18	104	32 (30.8)	58 (55.8)	14 (13.5)	122 (58.7)	86 (41.3)	267	113 (42.3)	118 (44.2)	36 (13.5)	344 (64.4)	190 (35.6)
Ma et al^Citation19	278	118 (42.4)	114 (41.0)	46 (16.5)	350 (62.9)	206 (37.1)	175	85 (48.6)	66 (37.7)	24 (13.7)	236 (67.4)	114 (32.6)
	Total	6A6A (%)	6A5A (%)	5A5A (%)	6A allele (%)	5A allele (%)	Total	6A6A (%)	6A5A (%)	5A5A (%)	6A allele (%)	5A allele (%)
rs3025058
Ghilardi et al^Citation16	41	18 (43.9)	17 (41.5)	6 (14.6)	53 (64.6)	29 (35.4)	133	38 (28.6)	59 (44.4)	36 (27.1)	135 (50.8)	131 (49.2)
Flex et al^Citation17	237	76 (32.1)	115 (48.5)	46 (19.4)	267 (56.3)	207 (43.7)	223	67 (30.0)	132 (59.2)	24 (10.8)	266 (59.6)	180 (40.4)
Ma et al^Citation19	270	162 (60.0)	91 (33.7)	17 (6.3)	415 (76.9)	125 (23.1)	170	116 (68.2)	50 (29.4)	4 (2.4)	282 (82.9)	58 (17.1)
Hao et al^Citation20	317	46 (14.5)	48 (15.1)	223 (70.3)	140 (22.1)	494 (77.9)	317	40 (12.6)	42 (13.2)	235 (74.1)	122 (19.2)	512 (80.8)
Zhao et al^Citation21	335	50 (14.9)	53 (15.8)	232 (69.3)	153 (22.8)	517 (77.2)	336	44 (13.1)	49 (14.6)	243 (72.3)	137 (20.4)	535 (79.6)
Huang et al^Citation22	640	482 (75.3)	151 (23.6)	7 (1.1)	1,115 (87.1)	165 (12.9)	637	540 (84.8)	94 (14.8)	3 (0.4)	1,174 (92.2)	100 (7.8)

Abbreviation: MMP-3, matrix metalloproteinase-3.

Figure 2 Forest plot for included studies examining the association between rs679620 and ischemic stroke risk under the dominant model (AA + GA vs GG).

Abbreviation: OR, odds ratio.

Table 3 Meta-analysis for the association of the MMP-3 polymorphisms rs679620 and rs3025058 with ischemic stroke risk

Polymorphism	Overall association			Association by ethnicity
	OR (95% CI)	P-value for pooled estimation	Test for heterogeneity, P-value	Asians			Caucasians
				OR (95% CI)	P-value for pooled estimation	Test for heterogeneity, P-value	OR (95% CI)	P-value for pooled estimation	Test for heterogeneity, P-value
rs679620
AA + GA vs GG	1.42 (1.05–1.91)	0.022	0.417	1.42 (1.05–1.91)	0.022	0.417	Not available	Not available	Not available
AA vs GA + GG	1.14 (0.76–1.73)	0.524	0.608	1.14 (0.76–1.73)	0.524	0.608	Not available	Not available	Not available
AA vs GG	1.38 (0.88–2.16)	0.161	0.991	1.38 (0.88–2.16)	0.161	0.991	Not available	Not available	Not available
A allele vs G allele	1.24 (1.00–1.54)	0.047	0.834	1.24 (1.00–1.54)	0.047	0.834	Not available	Not available	Not available
rs3025058
5A5A + 6A5A vs 6A6A	1.04 (0.73–1.47)	0.844	0.001	1.21 (0.81–1.79)	0.356	0.006	0.74 (0.43–1.27)	0.277	0.170
5A5A vs 6A5A + 6A6A	1.14 (0.74–1.77)	0.556	0.008	1.05 (0.69–1.58)	0.832	0.103	1.01 (0.24–4.25)	0.985	0.008
5A5A vs 6A6A	1.11 (0.68–1.80)	0.677	0.016	1.17 (0.68–2.00)	0.568	0.072	0.82 (0.18–3.80)	0.797	0.010
5A allele vs 6A allele	1.06 (0.79–1.41)	0.710	<0.001	1.16 (0.80–1.69)	0.433	<0.001	0.83 (0.42–1.66)	0.604	0.016

Abbreviations: OR, odds ratio; MMP-3, matrix metalloproteinase-3.

Figure 3 Forest plot for included studies examining the association between rs3025058 and ischemic stroke risk (5A5A + 6A5A vs 6A6A).

Note: Weights are from random-effects analysis.
Abbreviation: OR, odds ratio.

Figure 4 Sensitivity analysis for the association between rs3025058 and ischemic stroke risk (5A5A + 6A5A vs 6A6A).

KimSKKangSWKimDHYunDHChungJHBanJYMatrix metalloproteinase-3 gene polymorphisms are associated with ischemic strokeJ Interferon Cytokine Res2012322818622175304

 PubMed Web of Science ®Google Scholar

MaAJFanLYLiWJAssociation of matrix metalloproteinase-3 gene polymorphisms with subtypes of ischemic strokeChin J Med Genet201330461466

 Google Scholar

GhilardiGBiondiMLDeMontiMTurriOGuagnelliniEScorzaRMatrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with carotid artery stenosisStroke200233102408241212364729

 PubMed Web of Science ®Google Scholar

FlexAGaetaniEPapaleoPProinflammatory genetic profiles in subjects with history of ischemic strokeStroke200435102270227515308783

 PubMed Web of Science ®Google Scholar

HaoYTianSSunMZhuYNieZYangSAssociation between matrix metalloproteinase gene polymorphisms and development of ischemic strokeInt J Clin Exp Pathol201589116471165226617904

 PubMed Web of Science ®Google Scholar

ZhaoJHXuYMXingHXAssociations between matrix metalloproteinase gene polymorphisms and the development of cerebral infarctionGenet Mol Res2016144194181942426782596

 PubMed Web of Science ®Google Scholar

HuangXYHanLYHuangXDGuanCHMaoXLYeZSAssociation of matrix metalloproteinase-1 and matrix metalloproteinase-3 gene variants with ischemic stroke and its subtypeJ Stroke Cerebrovasc Dis201726236837527793533

 PubMed Web of Science ®Google Scholar