Significant association of BDNF rs6265 G>A polymorphism with susceptibility to epilepsy: a meta-analysis

Figures & data

Table 1 Characteristics of case–control studies on BDNF rs6265 G>A polymorphism and epilepsy risk included in the meta-analysis

First author	Year	Country/ethnicity	Control design	Genotyping method	Case	Control	Genotype distribution						P-value for HWEa	Type	AD	MAF
							Case			Control
							GG	GA	AA	GG	GA	AA
Kanemoto et al^Citation19	2003	Japan/Asian	Hospital control	PCR-RFLP	219	325	66	116	37	105	164	56	0.56	TLE+other	Adult	0.42
Chou et al^Citation28	2004	China/Asian	Healthy control	PCR-RFLP	103	83	29	46	28	16	38	29	0.29	Epilepsy	Child	0.58
Lohoff et al^Citation21	2005	US/Caucasian	Healthy control	Applied biosystems	151	189	109	35	7	124	57	8	0.66	TLE	Adult	0.19
Bragatti et al^Citation22	2010	Brazil/Caucasian	Healthy control	PCR-RFLP	101	104	73	28	0	74	30	0	0.09	TLE	Adult	0.14
Chen et al^Citation23	2011	China/Asian	Hospital control	PCR-RFLP	128	132	33	66	29	33	70	29	0.48	Epilepsy	Child	0.48
Tondo et al^Citation29	2011	Spain/Caucasian	NA	Applied biosystems	10	56	8	1	1	36	17	3	0.60	Epilepsy	Mixed	0.21
Fu et al^Citation24	2014	China/Asian	Hospital control	Direct sequencing	40	40	13	18	9	10	17	13	0.36	TLE+other	Child	0.54
Gkampeta et al^Citation25	2014	Greece/Caucasian	Healthy control	PCR-RFLP	60	60	38	19	3	32	24	4	0.86	Epilepsy	Child	0.27
Sha’ari et al^Citation26	2016	Malaysia+China/Asian	Healthy control	Illumina HumanHap	1,630	4,401	500	780	350	1,201	2,166	1,034	0.34	Epilepsy	Adult	0.48
Shen et al^Citation27	2016	China/Asian	Hospital control	Taqman	499	1,181	158	244	97	331	551	299	0.02	TLE	Adult	0.49

Note:

a HWE in control.

Abbreviations: AD, age distribution; HWE, Hardy-Weinberg equilibrium; MAF, minor allele frequency in control group; NA, not available; PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism; TLE, temporal lobe epilepsy.

Figure 1 Flow diagram of the study selection process.

Figure 2 OR and 95% CIs of the associations between BDNF rs6265 G>A polymorphism and epilepsy susceptibility in GA+AA vs GG model.

Table 2 Summary ORs and 95% CIs of BDNF rs6265 G>A polymorphism and epilepsy risk

rs6265 G>A	N*	A vs G				GA vs GG				AA vs GG				GA+AA vs GG				AA vs GG +GA
		OR	95% CI	P-value	I^2 (%)	OR	95% CI	P-value	I^2 (%)	OR	95% CI	P-value	I^2 (%)	OR	95% CI	P-value	I^2 (%)	OR	95% CI	P-value	I^2 (%)
Total	10	0.88	0.83–0.94	<0.01	0	0.88	0.79–0.97	0.01	0	0.79	0.70–0.90	<0.01	0	0.85	0.77–0.94	<0.01	0	0.85	0.76–0.95	0.01	0
HWE-yes	9	0.90	0.84–0.96	0.01	0	0.87	0.77–0.97	0.01	0	0.82	0.71–0.95	0.01	0	0.85	0.77–0.95	<0.01	0	0.89	0.79–1.01	0.07	0
Ethnicity
Asian	6	0.89	0.83–0.95	<0.01	0	0.89	0.80–0.99	0.04	0	0.79	0.69–0.90	<0.01	0	0.86	0.78–0.95	<0.01	0	0.85	0.76–0.95	0.01	0
Caucasian	4	0.82	0.62–1.08	0.15	0	0.73	0.52–1.03	0.07	0	0.92	0.40–2.08	0.84	0	0.76	0.55–1.04	0.09	0	1.04	0.46–2.34	0.92	0
Design
Hospital base	4	0.88	0.79–0.99	0.04	13.2	0.97	0.80–1.17	0.75	0	0.77	0.61–0.98	0.03	0	0.90	0.76–1.08	0.27	0	0.79	0.64–0.97	0.02	0
Healthy base**	5	0.88	0.82–0.95	<0.01	0	0.84	0.75–0.95	0.01	0	0.80	0.69–0.94	0.01	0	0.83	0.74–0.93	<0.01	0	0.88	0.77–1.01	0.06	0
NA	1	0.68	0.18–2.53	0.57	NA	0.26	0.03–2.29	0.23	NA	1.50	0.14–16.36	0.74	NA	0.45	0.09–2.33	0.34	NA	1.96	0.18–21.02	0.58	NA
Subtype
TLE	5	0.88	0.78–0.99	0.04	39.3	0.89	0.74–1.07	0.23	0	0.80	0.62–1.02	0.07	0	0.86	0.72–1.03	0.10	0	0.73	0.57–1.52	0.77	60.8
AD
Adult	5	0.89	0.83–0.95	<0.01	0	0.89	0.80–0.99	0.03	0	0.80	0.70–0.92	<0.01	0	0.86	0.78–0.95	<0.01	0	0.86	0.76–0.96	0.01	0
Children	4	0.82	0.66–1.03	0.09	0	0.78	0.54–1.13	0.20	0	0.71	0.45–1.12	0.14	0	0.75	0.53–1.07	0.11	0	0.81	0.55–1.18	0.28	0
Mixed	1	0.68	0.18–2.53	0.57	NA	0.26	0.03–2.29	0.23	NA	1.50	0.14–16.36	0.74	NA	0.45	0.09–2.33	0.34	NA	1.96	0.18–21.02	0.58	NA
Type
PCR-RFLP	5	0.94	0.79–1.10	0.43	0	0.94	0.73–1.21	0.63	0	0.88	0.61–1.26	0.48	0	0.92	0.73–1.17	0.52	0	0.91	0.67–1.23	0.53	0
Other	5	0.87	0.82–0.94	<0.01	0	0.86	0.77–0.97	0.01	0	0.78	0.68–0.90	<0.01	0	0.84	0.75–0.93	<0.01	0	0.85	0.75–0.95	0.01	0

Notes: Statistically significant values are shown in bold. I² for heterogeneity test.

* Numbers of comparisons.

** Healthy base refers to control groups that consist of healthy persons who may be from the hospital or from the general population.

Abbreviations: AD, age distribution; HWE, Hardy-Weinberg equilibrium; NA, not available; PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism; TLE, temporal lobe epilepsy.

Figure 3 Sensitivity analysis by removing one study at a time to reflect the influence of the individual dataset on the pooled ORs in GA+AA vs GG model of BDNF rs6265 G>A polymorphism.

Figure 4 Cumulative meta-analyses according to publication year in GA+AA vs GG model of BDNF rs6265 G>A polymorphism.

Figure 5 Funnel plot analysis to detect publication bias for GA+AA vs GG model of BDNF rs6265 G>A polymorphism.

Note: Circles represent the number of the studies.

Figure S1 OR and 95% CIs of the associations between BDNF rs6265 G>A polymorphism and epilepsy susceptibility (A for A vs G model; B for GA vs GG model; C for AA vs GG model; and D for AA vs GG+GA model).

Figure S2 Sensitivity analysis through deleting each study to reflect the influence of the individual dataset to the pooled ORs in BDNF rs6265 G>A polymorphism and epilepsy susceptibility (A for A vs G model; B for GA vs GG model; C for AA vs GG model; and D for AA vs GG+GA model).

Figure S3 Cumulative meta-analyses according to publication year in BDNF rs6265 G>A polymorphism and epilepsy susceptibility (A for A vs G model; B for GA vs GG model; C for AA vs GG model; and D for AA vs GG+GA model).

Figure S4 Funnel plot analysis to detect publication bias in BDNF rs6265 G>A polymorphism and epilepsy susceptibility (A for A vs G model; B for GA vs GG model; C for AA vs GG model; and D for AA vs GG+GA model).

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