title: Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis.
abstract: BACKGROUND
  The kynurenine (KYN) pathway has been shown to be altered in several diseases which compromise the central nervous system (CNS) including infectious diseases such as bacterial meningitis (BM). The aim of this study was to assess single nucleotide polymorphisms (SNPs) in four genes of KYN pathway in patients with meningitis and their correlation with markers of immune response in BM.
  
  
  METHODS
  One hundred and one individuals were enrolled in this study to investigate SNPs in the following genes: indoleamine-2,3-dioxygenase (IDO1 gene), kynureninase (KYNU gene), kynurenine aminotransferase I (CCBL1 gene), and kynurenine aminotransferase II (AADAT gene). SNP analyses were performed by primer-introduced restriction analysis-PCR (PIRA-PCR) followed by RFLP. Cytokines were measured using multiplex bead assay while immunoglobulins (IG) by immunodiffusion plates and NF-kappaB and c-Jun by dot blot assay.
  
  
  RESULTS
  The variant allele of SNP AADAT+401C/T showed prevalent frequency in patients with BM. A significant decrease (p < 0.05) in TNF-α, IL-1β, IL-6, MIP-1αCCL3 and MIP-1β/CCL4 levels was observed in BM patients homozygous (TT) to the SNP AADAT+401C/T. Furthermore, a significant (p < 0.05) decrease in cell count was observed in cerebrospinal fluid (CSF) from patients with TT genotype. In addition, an increase in the IgG level in adults (p < 0.05) was observed. The variant allele for KYNU+715G/A was found with low frequency in the groups, and the SNPs in IDO1+434T/G, KYNU+693G/A, CCBL1+164T/C, and AADAT+650C/T had no frequency in this population.
  
  
  CONCLUSIONS
  This study is the first report of an association of SNP AADAT+401C/T with the host immune response to BM, suggesting that this SNP may affect the host ability in recruitment of leukocytes to the infection site. This finding may contribute to identifying potential targets for pharmacological intervention as adjuvant therapy for BM.
authors.affiliation: Departamento de Biologia Celular e Genética, Universidade Federal do Rio Grande do Norte, Natal, Brazil.
authors.forename: Fladjule Rejane Soares
authors.initials: FR
authors.lastname: de Souza
authors.forename: Fabrícia Lima
authors.initials: FL
authors.lastname: Fontes
authors.forename: Thayse Azevedo
authors.initials: TA
authors.lastname: da Silva
authors.forename: Leonam Gomes
authors.initials: LG
authors.lastname: Coutinho
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
authors.forename: Lucymara Fassarella
authors.initials: LF
authors.lastname: Agnez-Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D018925:Chemokines / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000134:cerebrospinal fluid; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D008297:Male; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000637:Transaminases / Q000235:genetics*; D055815:Young Adult
chemical_list: D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D006867:Hydrolases; C021480:kynureninase