title: Severe preeclampsia: association of genes polymorphisms and maternal cytokines production in Brazilian population.
abstract: BACKGROUND
  Preeclampsia (PE) is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Healthy pregnancy is associated with a controlled inflammatory process, which is exacerbated in PE in response to excessive placental stimuli. Gene expression levels can affect inflammation and immune regulation. It is known that differences in cytokine allele frequencies amongst populations may contribute to difference in the incidence of several diseases.
  
  
  OBJECTIVE
  The aim of this study was to investigate the frequency of TNF-α, IL-6, IFN-γ and IL-10 genes polymorphisms and their relationship with the cytokines plasma levels in PE.
  
  
  METHODS
  A total of 281 women were included in this study; 116 with severe PE, 107 normotensive pregnant and 58 non-pregnant women. Cytokine genotyping was carried out by the polymerase chain reaction. The analyzed polymorphisms were: TNF-α (-308 G→A), IL-10 (-1082 G→A), IL-6 (-174 G→C), and IFN-γ (+874 A→T). Cytokine plasma levels were measured by Cytometric Bead Array method.
  
  
  RESULTS
  A higher frequency of the IFN-γ (+874) T/T genotype in severe PE comparing to normotensive pregnant women was found (P<0.001). TNF-α, IL-6 and IFN-γ plasma levels were higher in PE women compared to non-pregnant women (P<0.001; P<0.001; P=0.004). IL-6 and IFN-γ levels were also higher in PE women compared to normotensive pregnant (P<0.001; P=0.010). IL-10 levels were higher in normotensive pregnant women compared to PE (P<0.001). IFN-γ and IL-6 genes polymorphisms influenced the genic expression in PE and normotensive pregnant women, respectively.
  
  
  CONCLUSIONS
  These results suggest that IFN-γ seems to play a role in PE occurrence.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Faculdade de Medicina, Universidade Federal de São João Del Rei, Divinópolis, Minas Gerais, Brazil.
authors.forename: Melina B
authors.initials: MB
authors.lastname: Pinheiro
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: karinabgb@gmail.com.
authors.forename: Karina B
authors.initials: KB
authors.lastname: Gomes
authors.affiliation: Simile Instituto de Imunologia Aplicada, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Carla R S C
authors.initials: CR
authors.lastname: Ronda
authors.affiliation: Simile Instituto de Imunologia Aplicada, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Gabrielle G
authors.initials: GG
authors.lastname: Guimarães
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Letícia G
authors.initials: LG
authors.lastname: Freitas
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração - Centro de Pesquisas René Rachou-Fundação Osvaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração - Centro de Pesquisas René Rachou-Fundação Osvaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Luci M
authors.initials: LM
authors.lastname: Dusse
mesh_terms: D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Cytokine gene polymorphism; Cytokine levels; Inflammation; Preeclampsia