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Genetic polymorphisms associated with the inflammatory response in bacterial meningitis
Fabrícia Lima Fontes1, Luíza Ferreira de Araújo2, Leonam Gomes Coutinho3
1Departamento de Biologia Celular e Genética, Universidade Federal do Rio Grande do Norte, UFRN, Natal, Brazil. fontesfl@hotmail.com.
BMC Medical Genetics
|August 29, 2015
Summary
Genetic variations influence bacterial meningitis (BM) risk and inflammatory responses. Certain gene combinations may offer protection, aiding in understanding BM and developing new treatments.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Bacterial meningitis (BM) presents high mortality and morbidity, with neurological sequelae common despite antibiotic treatment.
- Adjuvant therapies are crucial for reducing sequelae in BM patients.
- Previous studies identified associations between specific single nucleotide polymorphisms (SNPs) and BM.
Purpose of the Study:
- To analyze the association between TNF -308G>A, TNF -857C>T, and IL-8 -251A>T SNPs and bacterial meningitis (BM).
- To investigate gene-gene interactions among previously identified and currently studied SNPs in relation to BM.
Main Methods:
- Genotyping of 54 BM patients and 110 healthy controls using PIRA-PCR or PCR-RFLP.
- Association analysis of allelic/genotypic frequencies with cytokine/chemokine levels (x-MAP) and cell counts.
- Gene-gene interaction analysis using generalized multifactor dimensionality reduction (GMDR).
Main Results:
- No significant association was found for TNF -857C>T and IL-8 -251A>T SNPs with BM.
- The variant allele TNF -308A showed higher frequency in controls, suggesting a potential protective role.
- Combined analysis revealed significant associations between specific genotypes (APEX1 148Glu, IL8 -251T, AADAT +401T) and BM, impacting inflammatory markers.
Conclusions:
- Genetic variability is significantly associated with altered inflammatory responses in BM.
- Understanding these genetic associations can improve insights into BM pathogenesis.
- This knowledge may contribute to developing novel therapeutic strategies for BM.
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