한국인 쯔쯔가무시병 환자에서 사이토카인 유전자의 다양성 조사
Investigation of Cytokine Gene Polymorphisms in Korean Patients with Scrub Typhus
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Scrub typhus is caused by Orientia tsutsugamushi and can become severe and potentially life-threatening. It is suggested that specific host factors can modify the host response during O. tsutsugamushi infection. It is known that susceptibility and outcome of infectious disease are associated with genetic polymorphisms of some cytokines. Materials and Methods: Peripheral blood of 144 patients who were diagnosed with scrub typhus and of 311 unrelated healthy subjects were collected. A diagnosis of scrub typhus was made upon demonstration of a fourfold rise in antibody titer to O. tsutsugamushi in paired serum specimens in an indirect immunofluorescent (IFA) test. Genomic DNAs were extracted from peripheral mononuclear cells and genotypings for IL-1 (-511C/T), IL-1β (+3953T/C), IL-2 (-330T/G), IL-4 (-590C/T), IL-4R(-1902G/A), IL-10 (-1082G/A), IL-10 (-819C/T), TNF-α (-238G/A) and TNF-α (-308G/A) were performed simultaneously using PCR-SSP (sequence specific polymorphisms) assay. Results: The frequency of IL-1 (-511T/T) (OR=0.53, P<0.01) and IL-2 (-330T/T) (OR=0.56, P<0.01) were significantly decreased, but that of IL-2(-330G/G) (OR=4.49, P<0.01) was increased, in the scrub typhus patients compared to the healthy controls. And, there were no statistically significant differences in the genetic polymorphisms of IL-4 (-590C/T), IL-4Rα (-1902G/A), IL-10 (-1082G/A), IL-10 (-819C/T), TNF-α (-238G/A), TNF-α (-308G/A) genes, in the scrub typhus patients compared to the unrelated healthy controls. Conclusions: Cytokine polymorphisms in the IL-1 (-511T/T) and the IL-2 genes may influence the host response to O. tsutsugamushi.
Abstract
Background: Scrub typhus is caused by Orientia tsutsugamushi and can become severe and potentially life-threatening. It is suggested that specific host factors can modify the host response during O. tsutsugamushi infection. It is known that susceptibility and outcome of infectious disease are associated with genetic polymorphisms of some cytokines. Materials and Methods: Peripheral blood of 144 patients who were diagnosed with scrub typhus and of 311 unrelated healthy subjects were collected. A diagnosis of scrub typhus was made upon demonstration of a fourfold rise in antibody titer to O. tsutsugamushi in paired serum specimens in an indirect immunofluorescent (IFA) test. Genomic DNAs were extracted from peripheral mononuclear cells and genotypings for IL-1 (-511C/T), IL-1β (+3953T/C), IL-2 (-330T/G), IL-4 (-590C/T), IL-4R(-1902G/A), IL-10 (-1082G/A), IL-10 (-819C/T), TNF-α (-238G/A) and TNF-α (-308G/A) were performed simultaneously using PCR-SSP (sequence specific polymorphisms) assay. Results: The frequency of IL-1 (-511T/T) (OR=0.53, P<0.01) and IL-2 (-330T/T) (OR=0.56, P<0.01) were significantly decreased, but that of IL-2(-330G/G) (OR=4.49, P<0.01) was increased, in the scrub typhus patients compared to the healthy controls. And, there were no statistically significant differences in the genetic polymorphisms of IL-4 (-590C/T), IL-4Rα (-1902G/A), IL-10 (-1082G/A), IL-10 (-819C/T), TNF-α (-238G/A), TNF-α (-308G/A) genes, in the scrub typhus patients compared to the unrelated healthy controls. Conclusions: Cytokine polymorphisms in the IL-1 (-511T/T) and the IL-2 genes may influence the host response to O. tsutsugamushi.
참고문헌 (16)
- Seong SY, "Orientia tsutsugamushi infection: overview and immune response", Microbes Infect, 3, pp.11~21 (2001)
- Iwasaki H, "Increased levels of macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha in sera of patients with Orientia tsutsugamushi infection", J Clin Microbiol, 35, pp.3320~3322 (1997)
- Ollier WE, "Cytokine genes and disease susceptibility", Cytokine, 28, pp.174~178 (2004)
- Arcaroli J, "Genetic polymorphisms and sepsis", Shock, 24, pp.300~312 (2005)
- Holmes CL, "Genetic polymorphism in sepsis and septic shock: role in prognosis and potential for therapy", Chest, 124, pp.1103~1115 (2003)
- Hyoung Doo Shin, "Common interleukin 10 polymorphism associated with decreased risk of tuberculosis", Experimental and Molecular Medicine, 37(2), pp.128~132 (2005), 생화학분자생물학회
- Wilson J, "Genetic variation at the IL 10 gene locus is associated with severity of respiratory syncytial virus bronchiolitis", J Infect Dis, 191, pp.1705~1709 (2005)
- Sallakci N, "TNF-alpha G-308A polymorphism is associated with rheumatic fever and correlates with increased TNF-alpha production", J Autoimmun, 25, pp.150~154 (2005)
- O’ Keefe GE, "The G-->A single nucleotide polymorphism at the -308 position in the tumor necrosis factoralpha promoter increases the risk for severe sepsis after trauma", J Trauma, 52, pp.817~825 (2002)
- Conti B, "Cytokines and fever", Front Biosci, 9, pp.1433~1449 (2004)
- Herrmann JL, "TNF alpha, IL-1 beta and IL-6 plasma levels in neutropenic patients after onset of fever and correlation with the C-reactive protein(CRP) kinetic values", Infection, 22, pp.309~315 (1994)
- Engel A, "Kinetics and correlation with body temperature of circulat ing interleukin-6, interleukin-8, tumor necrosis factor alpha and interleukin-1 beta in patients with fever and neutropenia", Infection, 22, pp.160~164 (1994)
- Schaaf BM, "Pneumococcal septic shock is associated with the interleukin-10-1082 gene promoter polymorphism", Am J Respir Crit Care Med, 168, pp.476~480 (2003)
- Smolnikova MV, "Association of IL2, TNFA, IL4 and IL10 promoter gene polymorphisms with the rate of progression of the HIV infection", Russ J Immunol, 7, pp.349~356 (2002)
- Iwasaki H, "Fulminant Japanese spotted fever associated with hypercytokinemia", J Clin Microbiol, 39, pp.2341~2343 (2001)
- Hulkkonen J, "A rare allele combination of the interleukin-1 gene complex is associated with high interleukin-1 beta plasma levels in healthy individuals", Eur Cytokine Netw, 11, pp.251~255 (2000)