A functional genetic variation in the protein Z (PROZ) gene — rs494860 — may contribute to the pathogenesis and risk for cerebral infarctions among patients with bacterial meningitis, according to the results of a nationwide prospective genetic association study conducted in The Netherlands and published in the Journal of Infection.
The investigators sought to explore whether genetic variation in coagulation and fibrinolytic genes are associated with cerebrovascular complications among individuals with bacterial meningitis. The prospective study was performed in patients ≥16 years of age with community-acquired bacterial meningitis. The presence of bacterial meningitis was confirmed by a positive culture of the patient’s cerebrospinal fluid (CSF) or blood, or by a positive result of a polymerase chain reaction test of the CSF in combination with specific CSF findings indicative of the disease.
The exons and flanking regions of 16 candidate genes that are known to be involved in coagulation and fibrinolysis pathways were sequenced. The researchers examined whether genetic variations among these genes are linked to a higher risk for cerebrovascular complications, differences in thrombocyte counts, and unfavorable outcomes on hospital admission.
Between 2006 and 2011, there were a total of 1101 patients with bacterial meningitis who were identified, of whom 622 supplied their DNA for genotyping and passed genetic quality control steps. In 22% (139 of 622) of the participants, their bacterial meningitis episode was complicated by the occurrence of a cerebral infarction. Moreover, 30% (188 of 622) of the patients with bacterial meningitis had an unfavorable outcome.
The functional variant rs494860 in the PROZ gene was identified as the factor having the strongest association with the occurrence of cerebral infarction among these patients (odds ratio 0.49; 95% CI, 0.33-0.73; P =5.2×10–4). When Bonferroni correction for multiple testing was used, there was no genetic variant found to be significantly associated with bacterial meningitis (P value threshold 2.7×10–4).
The investigators concluded that replication of the findings from this analysis in other patient cohort studies is warranted in order to further confirm these results and their utility in further elucidating the pathogenesis of bacterial meningitis.
Kloek AT, Khan HN, Valls Seron M, et al. Variation in coagulation and fibrinolysis genes evaluated for their contribution to cerebrovascular complications in adults with bacterial meningitis in the Netherlands [published online May 7, 2018]. J Infect.