Genetic variants of the MBL2 gene are associated with mortality in pneumococcal sepsis

详细信息	查看全文 | 推荐本文 |

• 作者：José ; Garnacho-Montero^a ; ^b ; ^{jgarnachom@telefonica.net} ; Emilio Garcí ; a-Cabrera^b ; ^c ; Rocio Jimé ; nez-Á ; lvarez^a ; Ana Dí ; az-Martí ; n^a ; Jaume Revuelto-Rey^a ; Javier Aznar-Martí ; n^b ; ^d ; Carmen Garnacho-Montero^e
• 关键词：Streptococcus pneumoniae ; Single-nucleotide polymorphisms ; Mortality
• 刊名：Diagnostic Microbiology and Infectious Disease
• 出版年：2012
• 期刊代码：79_07328893
• 类别：med
• 出版时间：May, 2012
• 卷：73
• 期：1
• 页码：39-44
• 文件大小：203 K

摘要

Studies evaluating associations between polymorphisms of innate immunity genes and prognosis of infectious diseases have yielded conflicting results. Our aim was to assess the impact on mortality of different genotypic variants of the innate immunity in patients with pneumococcal sepsis. All adults admitted to the hospital with diagnosis of sepsis caused by Streptococcus pneumoniae were enrolled and single-nucleotide polymorphisms (SNP) in mannose-binding lectin 2 (MBL2), toll-like receptor (TLR) 2, TLR4, and Fc纬 receptor IIa genes were genotyped. Underlying diseases, severity of illness, and antibiotic management were also recorded. We included 117 patients: 98 pneumonias (83.6%), 17 meningitis (14.5%), and 2 patients (1.9%) with primary pneumococcal bacteremia. Allelic variants of the MBL2 gene (individuals heterozygous or homozygous for one of the 3 allelic variants B, C, and D: AO/OO) were present in 37 patients (32%), T399I polymorphism in TLR4 in 19 (16.2%), TLR4 D299G/T399I in 11 (9.4%), TLR2 R753Q in 3 (2.5%), and Fc纬RIIa-R/R131 in 26 patients (23%). Factors associated independently with in-hospital mortality were SNP MBL2 AO/OO (adjusted hazard ratios [aHR] 3.2, 95%confidence interval [CI] 1.01-9.8) and septic shock (aHR 15.3, 95%CI 3.5-36.5), whereas first adequate antibiotic dose 鈮? h was a protective factor (aHR 0.2, 95%CI 0.06-0.8). SNP MBL2 AO/OO (aHR 2.2, 95%CI 1.1-8.1) remained as a variable independently associated with 90-day mortality. In conclusion, variant alleles in the MBL2 gene are independently associated with in-hospital and medium-term mortalities in patients admitted to the hospital with pneumococcal sepsis.