Disease Markers

Research Article

Apolipoprotein E ε4 Polymorphism as a Risk Factor for Ischemic Stroke: A Systematic Review and Meta-Analysis

Table 1

Main characteristics of studies associated with APOE polymorphisms and IS stroke included in this meta-analysis.


Study ID	Region	Criteria for IS	Genotyping method	Source of control	Characteristics and the counts of every genotype
Study ID	Region	Criteria for IS	Genotyping method	Source of control	Group	Sample size	Male/ (%)	Age(years)	ε2/ε2	ε2/ε3	ε2/ε4	ε3/ε3	ε3/ε4	ε4/ε4	ε2 allele	ε3 allele	ε4 allele

Wu et al., 2020 [19]	China	CT/MRI	PCR	H-B	Case	938	581 (61.9%)		2	63	18	684	156	15	85	1587	204	Y	8
Wu et al., 2020 [19]	China	CT/MRI	PCR	H-B	Control	1028	622 (60.5%)		9	131	13	763	106	6	162	1763	131	Y	8

Zhao et al., 2017 [20]	China	CT/MRI	PCR	H-B	Case	513	294 (57.3%)		3	63	7	347	85	8	76	842	108	Y	7
Zhao et al., 2017 [20]	China	CT/MRI	PCR	H-B	Control	514	288 (56.0%)		5	70	8	366	64	1	88	866	74	Y	7

Coen Herak et al., 2017 [21]	Croatia	CT/MRI	PCR	P-B	Case	73	48 (65.8%)		0	10	2	50	11	0	12	121	13	Y	8
Coen Herak et al., 2017 [21]	Croatia	CT/MRI	PCR	P-B	Control	100	63 (63.0%)		1	11	0	74	13	1	13	172	15	Y	8

Das et al., 2016 [22]	Indian	CT/MRI	PCR-RFLP	P-B	Case	620	434 (70.0%)		5	46	6	431	120	12	62	1028	150	Y	8
Das et al., 2016 [22]	Indian	CT/MRI	PCR-RFLP	P-B	Control	620	428 (69.0%)		5	50	4	436	113	12	64	1035	141	Y	8

Koopal et al., 2016 [23]	Netherlands	CT	PCR	P-B	Case	278	NA	NA	3	30	8	160	69	8	44	419	93	N	7
Koopal et al., 2016 [23]	Netherlands	CT	PCR	P-B	Control	4220	NA	NA	50	389	96	2422	1127	136	585	6360	1495	N	7

Luo et al., 2015 [24]	China	CT/MRI	PCR	H-B	Case	712	465 (65.3%)		4	93	13	494	101	7	114	1182	128	Y	7
Luo et al., 2015 [24]	China	CT/MRI	PCR	H-B	Control	774	418 (54.0%)		3	107	8	535	113	8	121	1290	137	Y	7

Wei et al., 2015 [25]	Malaysia	CT/MRI	PCR	P-B	Case	297	33 (11.1%)		8	68	23	137	54	7	107	396	91	Y	8
Wei et al., 2015 [25]	Malaysia	CT/MRI	PCR	P-B	Control	297	119 (40.0%)		4	12	27	163	89	2	47	427	120	Y	8

Yan et al., 2015 [26]	China	CT/MRI	PCR-RFLP	H-B	Case	580	387 (66.7%)		11	41	33	351	82	62	96	825	239	Y	8
Yan et al., 2015 [26]	China	CT/MRI	PCR-RFLP	H-B	Control	580	379 (65.3%)		61	54	49	354	33	29	225	795	140	Y	8

Chatzistefanidis et al., 2014 [27]	Greece	CT/MRI	PCR	H-B	Case	329	225 (68.4%)		3	36	3	227	56	4	45	546	67	Y	7
Chatzistefanidis et al., 2014 [27]	Greece	CT/MRI	PCR	H-B	Control	361	205 (56.8%)		2	24	8	278	47	2	36	627	59	Y	7
Atadzhanov et al., 2013 [28]	Zambian	CT	PCR	P-B	Case	23	NA		0	4	3	9	7	0	7	29	10	Y	9
Atadzhanov et al., 2013 [28]	Zambian	CT	PCR	P-B	Control	116	50 (41.4%)	NA	0	25	7	38	37	9	32	138	62	Y	9

Gelfand et al., 2013 [29]	America	CT/MRI	PCR-RFLP	H-B	Case	13	10 (77.0%)	NA	0	1	2	5	3	2	3	14	9	Y	8
Gelfand et al., 2013 [29]	America	CT/MRI	PCR-RFLP	H-B	Control	84	46 (55.0%)	NA	0	8	3	55	16	2	11	134	23	Y	8

Balcerzyk et al., 2010 [30]	Poland	CT/MRI	PCR	P-B	Case	72	42 (58.3%)		1	9	0	52	6	4	11	119	14	Y	7
Balcerzyk et al., 2010 [30]	Poland	CT/MRI	PCR	P-B	Control	71	41 (57.8%)		0	8	0	51	11	1	8	121	13	Y	7

Tamam et al., 2009 [31]	Turkey	CT/MRI	PCR	H-B	Case	65	NA	NA	0	7	2	50	5	1	9	112	9	Y	7
Tamam et al., 2009 [31]	Turkey	CT/MRI	PCR	H-B	Control	30	10 (33.3%)		0	1	1	25	2	1	2	53	5	Y	7

Tascilar et al., 2009 [32]	Turkey	CT/MRI	PCR	P-B	Case	85	51 (60.0%)		3	18	3	45	9	7	27	117	26	Y	7
Tascilar et al., 2009 [32]	Turkey	CT/MRI	PCR	P-B	Control	77	25 (32.5%)		3	16	7	40	9	2	29	105	20	Y	7

Wang et al., 2009 [33]	China	CT/MRI	PCR	H-B	Case	396	209 (52.8%)		16	98	60	124	87	11	190	433	169	N	7
Wang et al., 2009 [33]	China	CT/MRI	PCR	H-B	Control	396	202 (51.0%)		33	116	41	164	39	3	223	483	86	N	7

Lai et al., 2007 [34]	China	MRI	PCR	H-B	Case	257	164 (63.8%)		1	17	10	162	67	0	29	408	77	N	8
Lai et al., 2007 [34]	China	MRI	PCR	H-B	Control	112	54 (48.2%)		4	5	5	78	19	1	18	180	26	N	8

Parfenov et al., 2007 [35]	Yakutsk	CT/MRI	PCR	P-B	Case	107	69 (64.5%)		1	5	1	63	33	4	8	164	42	Y	8
Parfenov et al., 2007 [35]	Yakutsk	CT/MRI	PCR	P-B	Control	101	61 (59.4%)		1	15	3	58	22	2	20	153	29	Y	8

Kang and Lee.2006 [36]	Korea	MRI	PCR	H-B	Case	194	116 (59.8%)		0	24	0	126	44	0	24	320	44	Y	8
Kang and Lee.2006 [36]	Korea	MRI	PCR	H-B	Control	168	94 (55.9%)		2	18	0	128	19	1	22	293	21	Y	8
Gao et al., 2006 [37]	China	CT/MRI	PCR	H-B	Case	100	71 (71.0%)		1	11	0	75	13	0	13	174	13	Y	8
Gao et al., 2006 [37]	China	CT/MRI	PCR	H-B	Control	100	71 (71.0%)		1	13	0	80	6	0	15	179	6	Y	8

Baum et al., 2006 [38]	China	CT/MRI	PCR	P-B	Case	243	134 (54.5%)		7	39	6	155	32	4	59	381	46	Y	8
Baum et al., 2006 [38]	China	CT/MRI	PCR	P-B	Control	311	152 (45.2%)		2	60	6	203	39	1	70	505	47	Y	8

Pezzini et al., 2005 [39]	Italy	CT/MRI	PCR	H-B	Case	163	84 (51.5%)		2	12	1	109	38	1	17	268	41	Y	8
Pezzini et al., 2005 [39]	Italy	CT/MRI	PCR	H-B	Control	158	85 (53.8%)		0	16	1	120	21	0	17	277	22	Y	8

Cerrato et al., 2005 [40]	Italy	CT/MRI	PCR	P-B	Case	302	100 (33.1%)		9	31	0	230	28	4	49	519	36	Y	7
Cerrato et al., 2005 [40]	Italy	CT/MRI	PCR	P-B	Control	228	104 (33.1%)		3	25	1	158	37	4	32	378		Y	7

Jin et al., 2004 [41]	China	CT/MRI	PCR-RFLP	P-B	Case	226	129 (57.1%)		2	14	3	152	52	3	21	370	61	Y	8
Jin et al., 2004 [41]	China	CT/MRI	PCR-RFLP	P-B	Control	201	109 (54.2%)		2	17	2	156	22	2	23	351	28	Y	8

Duzenli et al., 2004 [42]	Turkey	CT	PCR	P-B	Case	62	NA	NA	0	8	1	52	1	0	9	113	2	Y	8
Duzenli et al., 2004 [42]	Turkey	CT	PCR	P-B	Control	126	61 (48.4%)		2	23	2	80	18	1	29	201	22	Y	8

Slowik et al., 2003 [43]	Poland	CT/MRI	Immuno-blotting	H-B	Case	71	49 (69.0%)		0	3	0	53	14	1	3	123	16	Y	7
Slowik et al., 2003 [43]	Poland	CT/MRI	Immuno-blotting	H-B	Control	30	19 (63.4%)		0	1	0	21	8	0	1	51	8	Y	7

Souza et al., 2003 [44]	Brazil	CT	PCR	P-B	Case	107	NA		0	5	0	93	8	1	5	199	10	Y	8
Souza et al., 2003 [44]	Brazil	CT	PCR	P-B	Control	100	NA		0	8	2	74	16	0	10	172	18	Y	8

Karttunen et al., 2002 [45]	Finland	CT/MRI	Immuno-blotting	P-B	Case	44	27 (61.4%)	15–60	0	3	1	27	13	0	4	70	14	Y	8
Karttunen et al., 2002 [45]	Finland	CT/MRI	Immuno-blotting	P-B	Control	104	59 (56.7%)	15–60	1	4	1	67	28	3	7	166	35	Y	8

Morrison et al., 2002 [46]	America	MRI	PCR	P-B	Case	400	NA	NA	1	48	19	199	118	15	69	564	167	Y	7
Morrison et al., 2002 [46]	America	MRI	PCR	P-B	Control	1104	NA	NA	5	148	39	596	288	28	197	1628	383	Y	7
MacLeod et al., 2001 [47]	Scotland	CT	PCR	P-B	Case	266	150 (56.4%)		1	29	7	170	56	3	38	425	69	Y	7
MacLeod et al., 2001 [47]	Scotland	CT	PCR	P-B	Control	225	94 (41.7%)		0	20	6	133	63	3	26	349	75	Y	7

Chowdhury et al., 2001 [48]	Bangladesh	CT	PCR	H-B	Case	147	116 (79.9%)		3	3	0	113	26	2	9	255	30	N	6
Chowdhury et al., 2001 [48]	Bangladesh	CT	PCR	H-B	Control	190	129 (67.7%)		3	6	1	149	29	2	13	333	34	N	6

Frikke-Schmidt et al., 2001 [49]	Denmark	CT	PCR	P-B	Case	738	282 (61.8%)		5	77	23	409	207	17	110	1102	264	Y	6
Frikke-Schmidt et al., 2001 [49]	Denmark	CT	PCR	P-B	Control	8938	4022 (45.0%)		45	1126	232	5050	2244	241	1448	13470	2958	Y	6

Catto et al., 2000 [50]	England	CT	PCR	P-B	Case	515	259 (50.3%)		0	61	8	321	115	10	69	818	143	Y	7
Catto et al., 2000 [50]	England	CT	PCR	P-B	Control	289	151 (52.2%)		0	37	7	170	69	6	44	446	88	Y	7

Kokubo et al., 2000 [51]	Japan	CT/MRI	PCR-RFLP	P-B	Case	201	NA	40–89	12	15	2	138	33	1	41	324	37	N	7
Kokubo et al., 2000 [51]	Japan	CT/MRI	PCR-RFLP	P-B	Control	1126	333 (29.7%)		11	73	8	819	202	13	103	1913	236	N	7

Peng et al., 1999 [52]	China	CT	PCR	H-B	Case	90	NA		0	13	1	55	19	2	14	142	24	Y	7
Peng et al., 1999 [52]	China	CT	PCR	H-B	Control	90	NA		1	16	1	63	8	1	19	150	11	Y	7

Ji et al., 1998 [53]	Japan	CT/MRI	PCR-RFLP	P-B	Case	123	NA		0	9	3	79	29	3	12	196	38	N	7
Ji et al., 1998 [53]	Japan	CT/MRI	PCR-RFLP	P-B	Control	117	NA		0	4	4	95	14	0	8	208	18	N	7

Margaglione et al., 1998 [54]	Italy	CT/MRI	PCR	P-B	Case	100	51 (51.0%)		1	10	0	59	24	6	12	152	36	Y	8
Margaglione et al., 1998 [54]	Italy	CT/MRI	PCR	P-B	Control	506	NA	NA	5	47	7	368	78	1	64	861	87	Y	8

Kessler et al., 1997 [55]	Germany	CT/MRI	PCR	H-B	Case	227	108 (47.6%)		2	31	5	132	50	7	40	345	69	Y	8
Kessler et al., 1997 [55]	Germany	CT/MRI	PCR	H-B	Control	225	108 (48.0%)		1	24	6	149	43	2	32	365	53	Y	8

Hachinski et al., 1996 [56]	Britain	CT/MRI	IF	P-B	Case	89	61 (67.8%)		1	13	1	47	24	3	16	131	31	Y	8
Hachinski et al., 1996 [56]	Britain	CT/MRI	IF	P-B	Control	89	NA		2	10	1	57	18	1	15	142	21	Y	8
Couderc et al., 1993 [57]	France	CT	IF	H-B	Case	69	36 (52.2%)		1	7	0	50	10	1	9	117	12	N	7
Couderc et al., 1993 [57]	France	CT	IF	H-B	Control	566	347 (61.3%)		8	60	5	377	109	7	81	923	128	N	7

Qian et al., 2012 [58]	China	CT/MRI	PCR	H-B	Case	152	87 (57.2%)		0	21	0	95	29	7	21	240	43	Y	9
Qian et al., 2012 [58]	China	CT/MRI	PCR	H-B	Control	40	13 (32.5%)		0	5	0	29	6	0	5	69	6	Y	9

Konialis et al., 2016 [59]	Greece	CT	PCR	H-B	Case	200	142 (72.0%)		0	10	3	145	39	3	13	339	48	Y	7
Konialis et al., 2016 [59]	Greece	CT	PCR	H-B	Control	159	76 (47.5%)		1	16	0	126	16	0	18	284	16	Y	7

Fayed et al., 2009 [60]	Egypt	CT/MRI	PCR-RFLP	H-B	Case	40	NA	NA	0	3	7	11	11	8	10	36	34	Y	6
Fayed et al., 2009 [60]	Egypt	CT/MRI	PCR-RFLP	H-B	Control	20	NA	NA	0	3	1	15	1	0	4	34	2	Y	6

Stankovic et al., 2004 [61]	Serbian	CT/MRI	PCR-RFLP	P-B	Case	65	NA	NA	0	6	0	39	18	2	6	102	22	Y	7
Stankovic et al., 2004 [61]	Serbian	CT/MRI	PCR-RFLP	P-B	Control	330	NA	NA	12	56	7	205	47	3	87	513	60	Y	7

Pedro-Botet et al., 1992 [62]	Spain	CT	PCR	P-B	Case	100	NA	NA	2	12	0	54	26	6	16	146	38	Y	7
Pedro-Botet et al., 1992 [62]	Spain	CT	PCR	P-B	Control	100	NA	NA	0	13	2	69	13	3	15	164	21	Y	7

Fekih-Mrissa et al., 2014 [63]	Tunisia	CT/MRI	PCR	P-B	Case	6	NA	NA	0	0	0	0	5	1	0	5	7	Y	7
Fekih-Mrissa et al., 2014 [63]	Tunisia	CT/MRI	PCR	P-B	Control	42	NA	NA	0	8	0	18	15	1	8	59	17	Y	7

Brewin et al., 2020 [64]	London	CT/MRI	Exome sequenc-ing	P-B	Case	47	NA	NA	0	5	8	14	14	6	13	47	34	Y	7
Brewin et al., 2020 [64]	London	CT/MRI	Exome sequenc-ing	P-B	Control	236	NA	NA	6	41	11	97	71	10	64	306	102	Y	7

Saidi et al., 2009 [65]	Tunisia	CT/MRI	PCR	P-B	Case	228	114 (50.0%)		0	14	25	74	87	28	39	249	168	Y	8
Saidi et al., 2009 [65]	Tunisia	CT/MRI	PCR	P-B	Control	323	177 (54.8%)		0	27	28	187	71	10	55	472	119	Y	8

Wen et al., 2006 [66]	China	MRI	PCR	P-B	Case	67	NA		4	7	2	41	11	2	17	100	17	Y	9
Wen et al., 2006 [66]	China	MRI	PCR	P-B	Control	134	NA	NA	2	24	3	89	15	1	31	217	20	Y	9

Giassakis et al., 2007 [67]	Greece	CT/MRI	PCR	P-B	Case	100	70 (70.0%)		NA	NA	NA	NA	NA	NA	12	166	22	Y	8
Giassakis et al., 2007 [67]	Greece	CT/MRI	PCR	P-B	Control	96	66 (68.8%)		NA	NA	NA	NA	NA	NA	10	169	13	Y	8
Nakata et al., 1997 [68]	Japan	CT/MRI	PCR	P-B	Case	55	25 (45.0%)		NA	NA	NA	NA	NA	NA	2	98	10	Y	7
Nakata et al., 1997 [68]	Japan	CT/MRI	PCR	P-B	Control	61	30 (49.0%)		NA	NA	NA	NA	NA	NA	7	110	5	Y	7

Szolnoki et al., 2002 [69]	Hungary	MRI	PCR	H-B	Case	689	356 (51.7%)		NA	NA	NA	NA	NA	NA	104	934	340	Y	7
Szolnoki et al., 2002 [69]	Hungary	MRI	PCR	H-B	Control	652	341 (52.3%)		NA	NA	NA	NA	NA	NA	118	1016	170	Y	7

Aalto-Setala et al., 1998 [70]	Finland	CT/MRI	IF	P-B	Case	231	NA	<60	NA	NA	NA	NA	NA	NA	17	350	95	Y	7
Aalto-Setala et al., 1998 [70]	Finland	CT/MRI	IF	P-B	Control	615	NA	20–55	NA	NA	NA	NA	NA	NA	74	861	295	Y	7

Artieda et al., 2008 [71]	Spain	CT/MRI	PCR	P-B	Case	152	NA				1	110			NA	NA	NA	Y	7
Artieda et al., 2008 [71]	Spain	CT/MRI	PCR	P-B	Control	215	NA	NA			1	164	ε3/ε4 + ε4/ε4 = 30		NA	NA	NA	Y	7

Schneider et al., 2005 [72]	America	CT	PCR	P-B	Case	76	NA	NA	; ;						NA	NA	NA	NA	7
Schneider et al., 2005 [72]	America	CT	PCR	P-B	Control	138	NA	NA	; ;						NA	NA	NA	NA	7

Li et al., 2016 [73]	China	CT/MRI	PCR	P-B	Case	164	113 (68.9%)		; ;						NA	NA	NA	Y	8
Li et al., 2016 [73]	China	CT/MRI	PCR	P-B	Control	109	64 (58.7%)		; ;						NA	NA	NA	Y	8

Age (years): different statistical patterns of age (mean and IQR, , or range) were extracted. CT: computerized tomography; MRI: magnetic resonance imaging; PCR: polymerase chain reaction; RFLP: restriction fragment length polymorphism; IS: ischemic stroke; : Hardy-Weinberg equilibrium; : Newcastle-Ottawa Scale; NA: not available; IF: isoelectric focusing; H-B: hospital based; P-B: population based.