SNPs in DNA repair genes associated to meningitis and host immune response

Silva, Thayse Azevedo da; Fontes, Fabrícia Lima; Coutinho, Leonam Gomes; Souza, Fladjule Rejane Soares de; Melo, Julliane Tamara Araújo de; Souto, Janeusa Trindade de; Leib, Stephen L.; Agnez-Lima, Lucymara Fassarella

doi:10.1016/j.mrfmmm.2011.05.012

Cited by 18 publications

(28 citation statements)

References 82 publications

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“…In relation to BM group, 53 patients had positive diagnosis: 16 were diagnosed with S. pneumoniae, 7 with N. meningitidis, 6 with other pathogens, and 24 without specified etiology (Table 1). These data are consistent with other papers published by our group [6,7].…”

Section: Study Subjects and Samplessupporting

confidence: 94%

“…Although different pathogens involved in the BM evolution are recognized by different toll-like receptors (TLRs), an overlap in the activation of the same inflammatory response which starts with the induction of MyD88 -a dependent pathway of nuclear factor kappa B (NF-κB) has been reported [5]. This finding corroborates the recent studies from our group showing a similar profile of inflammatory modulators during BM caused by S. pneumoniae and N. meningitidis [6,7].…”

Section: Introductionsupporting

confidence: 85%

“…The genomic DNA from patients was submitted to treatment with formamidopyrimidine DNA glycosylase (FPG) (New England Biolabs) as described by da Silva et al [6]. This enzyme is a functional analog of OGG1 in bacteria and acts as a bifunctional glycosylase that recognizes oxidized damage as 8-oxodG due to its β-lyase activity [23].…”

Section: Detection Of Fpg Sensitive Sitesmentioning

confidence: 99%

“…Human Cytokine/Chemokine Panel (MPXHCYTO-60k, Millipore) was used including a set of 12 cytokines and chemokines (TNF-α, IL-6, IL-1β, IL-2, INF-γ, IL-10, IL-1Ra, MIP-1α/CCL3, MIP-1β/CCL4, MCP-1/CCL2, G-CSF and IL-8/CXCL8). The samples were processed and measured in duplicates and according to the manufacturer's instructions [6,7]. This assay allowed for the quantification of cytokines and chemokines over a broad range of 3.2-10.000 pg/ml, using Bio-Plex manager 4.01 software.…”

Section: Measurement Of Inflammatory Mediatorsmentioning

confidence: 99%

“…In previous work, polymorphisms in base excision repair (BER) genes, main involved in the repair of oxidized DNA damage, such as APEX1, PARP-1 and OGG1 have been associated with regulation of immune response in BM [6,15]. However, none study of association between genetic variants in the X-ray repair protein crosscomplementing group 1 (XRCC1) gene, a key protein from BER which interacts with APEX1 and OGG1, and meningitis inflammation has been performed.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in DNA Repair Gene XRCC1 (Arg194Trp) and (Arg399Gln) and their Role in the susceptibility of Bacterial Meningitis

Pinheiro¹,

Fontes²,

Oliveira³

et al. 2015

J Meningitis

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Meningitis is a contagious infectious disease with high rates of mortality. Most pathogenic microbes in humans have the ability to cause bacterial meningitis. However, the most common pathogens are Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). It was found that the susceptibility to this infectious disease may be related to genetic characteristics of the host, such as the occurrence of single nucleotide polymorphisms (SNPs). In our previous work, association of SNPs in DNA repair genes with bacterial meningitis (BM) was demonstrated. In this study we evaluated two non-synonymous SNPs of the repair gene XRCC1 Arg194Trp (rs 1799782) and Arg399Gln (rs 25487) in patients with BM and health volunteers. The patient genotypes were investigated by PCR-RFLP. DNA damages were quantified using the genomic DNA with formamidopyrimidine DNA-glycosylase (FPG). Cytokines and chemokines were quantified from cerebrospinal fluid samples from BM patients. Concerning the SNP XRCC1 Arg194Trp, none association was found relation to BM. However, a higher frequency of heterozygous genotype for XRCC1 Arg399Gln was observed in the control group compared to the BM group (P = 0.043; OR = 0.426). DNA damage and cytokine/chemokines levels were not positively correlated with polymorphic genotypes. In conclusion, there is an indication that the SNP XRCC1 Arg399Gln could have a possible protective effect against BM.

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Section: Study Subjects and Samplessupporting

confidence: 94%