<i>TNFA</i> gene in Brazilian patients with hemorrhagic stroke or cerebral aneurysm

Many cerebrovascular diseases display a relation with inflammatory processes. Furthermore, the influence of several polymorphisms has been studied to improve the knowledge of physiological mechanisms of the nervous system.

Objectives:

The aim of this study was to identify if there was an association between a polymorphism in -308 position of the TNFA gene and the development of hemorrhagic stroke or aneurysm in Distrito Federal, Brazil.

Methods:

We collected the clinical information and the medical records from hemorrhagic stroke or aneurysm patients. The occurrence of stroke or aneurysm was confirmed by computed tomography (CT) or magnetic resonance image (MRI). The TNFA genotypes were determined by polymerase chain reaction restriction fragment length polymorphism.

Results:

The AG genotype appears to decrease the occurrence of hemorrhagic stroke or aneurysm in people between 45-63 years. Our study was the first to investigate this association in a Brazilian sample, although a previous report showed a similar effect with ischemic stroke in a Chinese population.

Conclusion:

The TNFA -308 AG genotype is associated with a decreased risk of aneurysm or hemorrhagic stroke in a population from the capital of Brazil, Distrito Federal.

Key words:
tumor necrosis factor-alpha; single nucleotide polymorphism; stroke; intracranial hemorrhages; intracranial aneurysm

	Aneurysm		HS		Control
	n	%	n	%	n	%	p-value
GG	21	63.6	37	77.1	47	58	0.09
AG	3	9.1	3	6.3	15	18.5	0.102
AA	9	27.3	8	16.7	19	23.5	0.493
Allele
G	45	68.2	77	80.2	109	67.3	0.07
A	21	31.8	19	19.8	53	32.7

	Aneurysm/HS		Control
	n	%	n	%	OR (CI)	p-value
GG	58	71.6	47	58	1.82 (0.95-3.51)	0.07
AG	6	7.4	15	18.5	0.35 (0.13-0.96)	0.035^*
AA	17	21	19	23.5	0.87 (0.41-1.82)	0.708
Allele
G	122	75.3	109	67.3	1.48 (0.91-2.41)	0.11
A	40	24.7	53	32.7	0.67 (0.41-1.09)	0.11

TNFA -308G/A
		GG						AG + AA
		Aneurysm/HS		Control				Aneurysm/HS		Control
		n	%	n	%	OR (CI)	p-value	n	%	n	%	OR (CI)	p-value
SAH	Yes	41	70.7	7	14.9	13.78 (5.16-36.79)	< 0.001^*	19	82.6	1	2.9	156.75 (16.31-1506.47)	< 0.001^*
SAH	No	17	.3 9. 2	40	85.1	13.78 (5.16-36.79)	< 0.001^*	4	17.4	33	97.1	156.75 (16.31-1506.47)	< 0.001^*
Smoking status	Yes	24	41.4	16	34	1.36 (0.61-3.04)	0.442	8	34.8	8	23.5	1.73 (0.54-5.57)	0.354
Smoking status	No	34	58.6	31	66	1.36 (0.61-3.04)	0.442	15	65.2	26	76.5	1.73 (0.54-5.57)	0.354
Alcohol consumption	Yes	15	CNJ	10	21.3	1.29 (0.52-3.21)	0.584	7	30.4	10	29.4	1.05 (0.33-3.33)	0.92
Alcohol consumption	No	43	74.1	37	78.7	1.29 (0.52-3.21)	0.584	16	69.6	24	70.6	1.05 (0.33-3.33)	0.92

		GG		AG + AA
		n	%	n	%	p
	Intermediate coma	5	8.6	3	13
Glasgow	Superficial coma	1	1.7	1	4.3	0.644
	Normality	52	89.7	19	82.6
	No symptoms at all	17	29.3	3	13
	No significant symptoms	32	55.2	14	60.9
	Slight disability	2	3.4	0	0
Rankin scale	Moderate disability	1	1.7	2	8.7	0.091
	Moderately severe disability	5	8.6	1	4.3
	Severe disability	1	1.7	3	13
	Severe disability	6	10.3	4	17.4
	Moderate disability	5	8.6	1	4.3
Barthel index	Slight disability	28	48.3	11	47.8	0.778
	Functional independence	19	32.8	7	30.4

		ß	E.P	Wald	gl	p	Exp(ß)	95% CI (EXP[ß])
		ß	E.P	Wald	gl	p	Exp(ß)	Lower	Upper
Step 1^a	Systemic arterial hypertension⁽¹⁾	0.659	0.667	0.974	1	0.324	1.933	0.522	7.15
	Smoking status⁽¹⁾	-0.012	0.56	0	1	4 8 .9 0.	0.988	0.33	2.965
	Alcohol consumption⁽¹⁾	0.316	0.558	0.321	1	0.571	1.372	0.459	4.098
	Rankin scale⁽¹⁾	0.631	0.722	0.762	1	0.383	1.879	0.456	7.74
	Constant	-1.603	0.723	4.91	1	0.027^*	0.201

	GG		AG + AA
	n	%	n	%	p-value
Middle cerebral artery	8	20.5	4	10.3	0.371
Right frontal parietal cavernous hemangioma	0	0	1	2.6
Aneurysm clip with post-surgery infection	1	2.6	0	0
Left temporal intraparenchymal hematoma	3	7.7	3	7.7
Subarachnoid hemorrhage	19	48.7	5	12.8
Diffuse subarachnoid hemorrhage	1	2.6	0	0
Thalamic hemorrhage with ventricular flood	1	2.6	0	0
Expansive point angle lesion	3	7.7	0	0
Basal ganglia	3	7.7	0	0

Sociedade Brasileira de Patologia Clínica, Rua Dois de Dezembro,78/909 - Catete, CEP: 22220-040v - Rio de Janeiro - RJ, Tel.: +55 21 - 3077-1400 / 3077-1408, Fax.: +55 21 - 2205-3386 - Rio de Janeiro - RJ - Brazil
E-mail: jbpml@sbpc.org.br

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[1] CORRESPONDING AUTHOR. Izabel Cristina Rodrigues da Silva, Campus Universitário; Centro Metropolitano; Ceilândia Sul; CEP: 72220-275; Brasília-DF, Brasil; e-mail: felipe.sab@hotmail.com.