title: Association of alpha-thalassemia, TNF-alpha (-308G>A) and VCAM-1 (c.1238G>C) gene polymorphisms with cerebrovascular disease in a newborn cohort of 411 children with sickle cell anemia.
abstract: Cerebrovascular disease (CVD) is a severe complication associated with sickle cell anemia. Abnormal transcranial Doppler (TCD) identifies some children at high risk, but other markers would be helpful. This cohort study was aimed at evaluating the effects of genetic biomarkers on the risk of developing CVD in children from Minas Gerais, Brazil. Clinical and hematological data were retrieved from children's records. Outcomes studied were overt ischemic stroke and CVD (overt ischemic stroke, transient ischemic attack, abnormal TCD, or abnormal cerebral angiography). Out of 411 children, 386 (93.9%) had SS genotype, 23 (5.6%) had Sβ(0)-thal and two had severe Sβ(+)-thal (0.5%). Frequency of CVD was lower in Sβ-thal group (p=0.05). No effect of VCAM-1 polymorphism on stroke or CVD risks was detected. Cumulative incidence of stroke was significantly higher for children with TNF-α A allele (p=0.02) and lower for children with HBA deletion (p=0.02). However, no association between CVD and TNF-α -308G>A was found. CVD cumulative incidence was significantly lower for children with HBA deletion (p=0.004). This study found no association between VCAM1 c.1238G>C and stroke. An association between stroke and TNF-α -308A allele has been suggested. Our results have confirmed the protective role of HBA deletion against stroke and CVD.
authors.affiliation: Centro de Tecidos Biológicos de Minas Gerais, Fundação Hemominas, Lagoa Santa, Minas Gerais, Brazil; Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. Electronic address: andrebelisario@yahoo.com.br.
authors.forename: André Rolim
authors.initials: AR
authors.lastname: Belisário
authors.affiliation: Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. Electronic address: fredericoln@gmail.com.
authors.forename: Frederico Lisboa
authors.initials: FL
authors.lastname: Nogueira
authors.affiliation: Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil. Electronic address: rahyssa_rodrigues@yahoo.com.br.
authors.forename: Rahyssa Sales
authors.initials: RS
authors.lastname: Rodrigues
authors.affiliation: Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil. Electronic address: nayara_005@yahoo.com.br.
authors.forename: Nayara Evelin
authors.initials: NE
authors.lastname: Toledo
authors.affiliation: Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil. Electronic address: analuizacattabriga@hotmail.com.
authors.forename: Ana Luiza Moreira
authors.initials: AL
authors.lastname: Cattabriga
authors.affiliation: Departmento Básico - Área de Saúde, Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, Minas Gerais, Brazil. Electronic address: cvbiogenet@yahoo.com.br.
authors.forename: Cibele
authors.initials: C
authors.lastname: Velloso-Rodrigues
authors.affiliation: Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. Electronic address: focduarte@gmail.com.
authors.forename: Filipe Otávio Chaves
authors.initials: FO
authors.lastname: Duarte
authors.affiliation: Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil; Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil. Electronic address: celia.cmaria@gmail.com.
authors.forename: Célia Maria
authors.initials: CM
authors.lastname: Silva
authors.affiliation: Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. Electronic address: vianamb@gmail.com.
authors.forename: Marcos Borato
authors.initials: MB
authors.lastname: Viana
mesh_terms: D000483:Alleles; D000755:Anemia, Sickle Cell / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006441:Hemoglobin A / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D020521:Stroke / Q000209:etiology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*; D017085:alpha-Thalassemia / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D006441:Hemoglobin A
keywords: Alpha-thalassemia; Sickle cell anemia; Stroke; TNF-alpha; VCAM-1