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

da Silva, Thayse Azevedo; Fontes, Fabrícia Lima; Coutinho, Leonam Gomes; de Souza, Fladjule Rejane Soares; de Melo, Julliane Tamara Araújo; de Souto, Janeusa Trindade; Leib, Stephen L.; Agnez-Lima, Lucymara Fassarella (2011). SNPs in DNA repair genes associated to meningitis and host immune response. Mutation research - fundamental and molecular mechanisms of mutagenesis, 713(1-2), pp. 39-47. Amsterdam: Elsevier 10.1016/j.mrfmmm.2011.05.012

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In vitro and in animal models, APE1, OGG1, and PARP-1 have been proposed as being involved with inflammatory response. In this work, we have investigated if the SNPs APE1 Asn148Glu, OGG1 Ser326Cys, and PARP-1 Val762Ala are associated to meningitis. The patient genotypes were investigated by PIRA-PCR or PCR-RFLP. DNA damages were detected in genomic DNA by Fpg treatment. IgG and IgA were measured from plasma and the cytokines and chemokines were measured from cerebrospinal fluid samples using Bio-Plex assays. A higher frequency (P<0.05) of APE1 Glu allele in bacterial meningitis (BM) and aseptic meningitis (AM) patients was observed. The genotypes Asn/Asn in control group and Asn/Glu in BM group was also higher. For the SNP OGG1 Ser326Cys, the genotype Cys/Cys was more frequent (P<0.05) in BM group. The frequency of PARP-1 Val/Val genotype was higher in control group (P<0.05). The occurrence of combined SNPs is significantly higher in BM patients, indicating that these SNPs may be associated to the disease. Increasing in sensitive sites to Fpg was observed in carriers of APE1 Glu allele or OGG1 Cys allele, suggesting that SNPs affect DNA repair activity. Alterations in IgG production were observed in the presence of SNPs APE1 Asn148Glu, OGG1 Ser326Cys or PARP-1 Val762Ala. Moreover, reduction in the levels of IL-6, IL-1Ra, MCP-1/CCL2 and IL-8/CXCL8 was observed in the presence of APE1 Glu allele in BM patients. In conclusion, we obtained indications of an effect of SNPs in DNA repair genes on the regulation of immune response in meningitis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Leib, Stephen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0027-5107

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:24

Last Modified:

27 Jul 2015 08:28

Publisher DOI:

10.1016/j.mrfmmm.2011.05.012

PubMed ID:

21651918

Web of Science ID:

000293930400005

BORIS DOI:

10.7892/boris.8286

URI:

https://boris.unibe.ch/id/eprint/8286 (FactScience: 213803)

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