Variation in coagulation and fibrinolysis genes evaluated for their contribution to cerebrovascular complications in adults with bacterial meningitis in the Netherlands
| Autor: | Bart Ferwerda, Hina N. Khan, Aldo Jongejan, M. Valls Seron, Frank Baas, Mieke C. Brouwer, A. van der Ende, Anne T. Kloek, D. van de Beek, Aeilko H. Zwinderman |
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| Přispěvatelé: | AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Graduate School, Neurology, Epidemiology and Data Science, APH - Methodology, Medical Microbiology and Infection Prevention, ARD - Amsterdam Reproduction and Development, APH - Personalized Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Microbiology (medical) Candidate gene medicine.medical_specialty medicine.medical_treatment Bacterial meningitis Protein Z 030204 cardiovascular system & hematology Meningitis Bacterial Cohort Studies 03 medical and health sciences 0302 clinical medicine Internal medicine Fibrinolysis Genetic variation Odds Ratio medicine Humans Prospective Studies Genotyping Genetic Association Studies Aged Netherlands Genetic association Meningitis Pneumococcal Cerebral infarction business.industry Sequence analysis Cerebral Infarction Sequence Analysis DNA Odds ratio Middle Aged Blood coagulation medicine.disease Community-Acquired Infections Cerebrovascular Disorders Infectious Diseases Female business 030217 neurology & neurosurgery |
| Zdroj: | Journal of infection, 77(1), 54-59. W.B. Saunders Ltd Journal of Infection, 77(1), 54-59 Journal of Infection |
| ISSN: | 0163-4453 |
| DOI: | 10.1016/j.jinf.2018.03.007 |
| Popis: | Summary Objective To study whether genetic variation in coagulation and fibrinolysis genes contributes to cerebrovascular complications in bacterial meningitis. Methods We performed a nationwide prospective genetic association study in adult community-acquired bacterial meningitis patients. The exons and flanking regions of 16 candidate genes involved in coagulation and fibrinolysis pathways were sequenced. We analyzed whether genetic variation in these genes resulted in a higher risk of cerebrovascular complications, unfavorable outcome and differences in thrombocyte count on admission. Results From 2006 to 2011, a total of 1101 bacterial meningitis patients were identified of whom 622 supplied DNA for genotyping and passed genetic quality control steps. In 139 patients (22%) the episode of bacterial meningitis was complicated by cerebral infarction, and 188 (30%) had an unfavorable outcome. We identified the functional variant rs494860 in the protein Z (PROZ) gene as our strongest association with occurrence of cerebral infarction (odds ratio (OR) 0.49 (95% confidence interval 0.33–0.73), p = 5.2 × 10 −4 ). After Bonferroni correction for multiple testing no genetic variant was significantly associated ( p -value threshold 2.7 × 10 −4 ). Conclusion Our study suggests a functional genetic variation in the PROZ gene, rs494860, may be of importance in bacterial meningitis pathogenesis and cerebral infarction risk. Replication of this finding in other cohort studies populations is needed. |
| Databáze: | OpenAIRE |
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