Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women
| Autor: | Sue Li, Marta Janer, Hongwei Wang, Ann E. Stapleton, Thomas R. Hawn, Walter E. Stamm, Alan Aderem, Thomas M. Hooton, Lue Ping Zhao, Delia Scholes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Candidate gene Bacteriuria Neutrophils Urinary system Immunology/Innate Immunity Population lcsh:Medicine Urine Biology Infectious Diseases/Urological Infections Polymorphism Single Nucleotide Asymptomatic Receptors Interleukin-8B Receptors Interleukin-8A Polymorphism (computer science) Gram-Negative Bacteria medicine Humans Urinary Tract education lcsh:Science Demography education.field_of_study Multidisciplinary Interleukin-8 lcsh:R Genetic Variation Odds ratio medicine.disease Immunity Innate Toll-Like Receptor 2 Immunology Female lcsh:Q Chemokines medicine.symptom Immunology/Genetics of the Immune System Research Article |
| Zdroj: | PLoS ONE, Vol 4, Iss 12, p e8300 (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | BACKGROUND:Although several studies suggest that genetic factors are associated with human UTI susceptibility, the role of DNA variation in regulating early in vivo urine inflammatory responses has not been fully examined. We examined whether candidate gene polymorphisms were associated with altered urine inflammatory profiles in asymptomatic women with or without bacteriuria. METHODOLOGY:We conducted a cross-sectional analysis of asymptomatic bacteriuria (ASB) in 1,261 asymptomatic women ages 18-49 years originally enrolled as participants in a population-based case-control study of recurrent UTI and pyelonephritis. We genotyped polymorphisms in CXCR1, CXCR2, TLR1, TLR2, TLR4, TLR5, and TIRAP in women with and without ASB. We collected urine samples and measured levels of uropathogenic bacteria, neutrophils, and chemokines. PRINCIPAL FINDINGS:Polymorphism TLR2_G2258A, a variant associated with decreased lipopeptide-induced signaling, was associated with increased ASB risk (odds ratio 3.44, 95%CI; 1.65-7.17). Three CXCR1 polymorphisms were associated with ASB caused by gram-positive organisms. ASB was associated with urinary CXCL-8 levels, but not CXCL-5, CXCL-6, or sICAM-1 (P< or =0.0001). Urinary levels of CXCL-8 and CXCL-6, but not ICAM-1, were associated with higher neutrophil levels (P< or =0.0001). In addition, polymorphism CXCR1_G827C was associated with increased CXCL-8 levels in women with ASB (P = 0.004). CONCLUSIONS:TLR2 and CXCR1 polymorphisms were associated with ASB and a CXCR1 variant was associated with urine CXCL-8 levels. These results suggest that genetic factors are associated with early in vivo human bladder immune responses prior to the development of symptomatic UTIs. |
| Databáze: | OpenAIRE |
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