Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis
<p>Abstract</p> <p><b>Background</b></p> <p>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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-04-01
|
| Series: | BMC Medical Genetics |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1471-2350/12/51 |
| _version_ | 1818950050531770368 |
|---|---|
| author | Leib Stephen L Coutinho Leonam da Silva Thayse Fontes Fabrícia de Souza Fladjule Agnez-Lima Lucymara |
| author_facet | Leib Stephen L Coutinho Leonam da Silva Thayse Fontes Fabrícia de Souza Fladjule Agnez-Lima Lucymara |
| author_sort | Leib Stephen L |
| collection | DOAJ |
| description | <p>Abstract</p> <p><b>Background</b></p> <p>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.</p> <p>Methods</p> <p>One hundred and one individuals were enrolled in this study to investigate SNPs in the following genes: indoleamine-2,3-dioxygenase (<it>IDO1 </it>gene), kynureninase (<it>KYNU </it>gene), kynurenine aminotransferase I (<it>CCBL1 </it>gene), and kynurenine aminotransferase II (<it>AADAT </it>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.</p> <p>Results</p> <p>The variant allele of SNP <it>AADAT</it>+401C/T showed prevalent frequency in patients with BM. A significant decrease (<it>p </it>< 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 <it>AADAT</it>+401C/T. Furthermore, a significant (<it>p </it>< 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 (<it>p </it>< 0.05) was observed. The variant allele for <it>KYNU</it>+715G/A was found with low frequency in the groups, and the SNPs in <it>IDO1</it>+434T/G, <it>KYNU</it>+693G/A, <it>CCBL1</it>+164T/C, and <it>AADAT</it>+650C/T had no frequency in this population.</p> <p><b>Conclusions</b></p> <p>This study is the first report of an association of SNP <it>AADAT</it>+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.</p> |
| first_indexed | 2024-12-20T09:12:25Z |
| format | Article |
| id | doaj.art-34a5f0b50f6e49f59e18597846c58595 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-20T09:12:25Z |
| publishDate | 2011-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-34a5f0b50f6e49f59e18597846c585952022-12-21T19:45:31ZengBMCBMC Medical Genetics1471-23502011-04-011215110.1186/1471-2350-12-51Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitisLeib Stephen LCoutinho Leonamda Silva ThayseFontes Fabríciade Souza FladjuleAgnez-Lima Lucymara<p>Abstract</p> <p><b>Background</b></p> <p>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.</p> <p>Methods</p> <p>One hundred and one individuals were enrolled in this study to investigate SNPs in the following genes: indoleamine-2,3-dioxygenase (<it>IDO1 </it>gene), kynureninase (<it>KYNU </it>gene), kynurenine aminotransferase I (<it>CCBL1 </it>gene), and kynurenine aminotransferase II (<it>AADAT </it>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.</p> <p>Results</p> <p>The variant allele of SNP <it>AADAT</it>+401C/T showed prevalent frequency in patients with BM. A significant decrease (<it>p </it>< 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 <it>AADAT</it>+401C/T. Furthermore, a significant (<it>p </it>< 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 (<it>p </it>< 0.05) was observed. The variant allele for <it>KYNU</it>+715G/A was found with low frequency in the groups, and the SNPs in <it>IDO1</it>+434T/G, <it>KYNU</it>+693G/A, <it>CCBL1</it>+164T/C, and <it>AADAT</it>+650C/T had no frequency in this population.</p> <p><b>Conclusions</b></p> <p>This study is the first report of an association of SNP <it>AADAT</it>+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.</p>http://www.biomedcentral.com/1471-2350/12/51Kynurenine PathwayPolymorphismMeningitisInflammatory response |
| spellingShingle | Leib Stephen L Coutinho Leonam da Silva Thayse Fontes Fabrícia de Souza Fladjule Agnez-Lima Lucymara Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis BMC Medical Genetics Kynurenine Pathway Polymorphism Meningitis Inflammatory response |
| title | Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis |
| title_full | Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis |
| title_fullStr | Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis |
| title_full_unstemmed | Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis |
| title_short | Association of kynurenine aminotransferase II gene C401T polymorphism with immune response in patients with meningitis |
| title_sort | association of kynurenine aminotransferase ii gene c401t polymorphism with immune response in patients with meningitis |
| topic | Kynurenine Pathway Polymorphism Meningitis Inflammatory response |
| url | http://www.biomedcentral.com/1471-2350/12/51 |
| work_keys_str_mv | AT leibstephenl associationofkynurenineaminotransferaseiigenec401tpolymorphismwithimmuneresponseinpatientswithmeningitis AT coutinholeonam associationofkynurenineaminotransferaseiigenec401tpolymorphismwithimmuneresponseinpatientswithmeningitis AT dasilvathayse associationofkynurenineaminotransferaseiigenec401tpolymorphismwithimmuneresponseinpatientswithmeningitis AT fontesfabricia associationofkynurenineaminotransferaseiigenec401tpolymorphismwithimmuneresponseinpatientswithmeningitis AT desouzafladjule associationofkynurenineaminotransferaseiigenec401tpolymorphismwithimmuneresponseinpatientswithmeningitis AT agnezlimalucymara associationofkynurenineaminotransferaseiigenec401tpolymorphismwithimmuneresponseinpatientswithmeningitis |