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

Abstract

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.