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Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 12/2015

01.12.2015 | Original Article

-572 G/C single nucleotide polymorphism of interleukin-6 and sepsis predisposition in chronic renal disease

verfasst von: A. Panayides, A. Ioakeimidou, V. Karamouzos, N. Antonakos, I. Koutelidakis, G. Giannikopoulos, K. Makaritsis, N. Voloudakis, K. Toutouzas, N. Rovina, M. Bristianou, G. Damoraki, C. Routsi, E. J. Giamarellos-Bourboulis, on behalf of the Hellenic Sepsis Study Group

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 12/2015

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Abstract

Single nucleotide polymorphisms (SNPs) of interleukin (IL)-6 are associated with the development of chronic renal disease (CRD). Their impact for sepsis in the field of CRD was investigated. One control cohort of 115 patients with CRD without infection and another case cohort of 198 patients with CRD and sepsis were enrolled. Genotyping at the −174 (rs1800795) and −572 positions of IL-6 (rs1800796) was done by restriction fragment length polymorphism. Circulating IL-6 was measured by an enzyme immunoassay. The GG genotype of rs1800796 was more frequent among cases (78.3 %) than controls (62.6 %). No difference in the genotype frequencies of rs1800795 between cases and controls were found. Odds ratio for sepsis was 2.07 (95%CI 1.24–3.44, p = 0.005) with the GG genotype of rs1800796, which was confirmed by logistic regression analysis taking into consideration the presence of chronic comorbidities. All-cause mortality until day 28 was similar between patients with the GG genotype and the GC/CC genotypes of rs1800796, but death caused from cardiovascular events not-related with infection was more frequent with the GG genotype (14.6 % vs 2.4 %, p = 0.031). Circulating IL-6 was greater among patients of the GC/CC genotypes of rs1800796 and multiple organ dysfunction (p = 0.013). The GG genotype of rs1800796 predisposes to sepsis in CRD and to 28-day mortality by sepsis-unrelated cardiovascular phenomena.
Literatur
1.
Zurück zum Zitat Stenvinkel P, Ketteler M, Johnson JRJ, Lindholm B, Pecoits-Filho R, Riella M, Heimbürger O, Cederholm T, Girndt M (2005) IL-10, IL-6, and TNF-a. Central factors in the altered cytokine network of uremia. The good, the bad, and the ugly. Kidney Int 67:1216–1233CrossRefPubMed Stenvinkel P, Ketteler M, Johnson JRJ, Lindholm B, Pecoits-Filho R, Riella M, Heimbürger O, Cederholm T, Girndt M (2005) IL-10, IL-6, and TNF-a. Central factors in the altered cytokine network of uremia. The good, the bad, and the ugly. Kidney Int 67:1216–1233CrossRefPubMed
2.
Zurück zum Zitat Hasuike Y, Nonoguchi H, Ito K, Naka M, Kitamura R, Nanami M, Tokuyama M, Kida A, Otaki Y, Kuragano T, Nakanishi T (2009) Interleukin-6 is a predictor of mortality in stable hemodialysis patients. Am J Nephrol 30:389–398CrossRefPubMed Hasuike Y, Nonoguchi H, Ito K, Naka M, Kitamura R, Nanami M, Tokuyama M, Kida A, Otaki Y, Kuragano T, Nakanishi T (2009) Interleukin-6 is a predictor of mortality in stable hemodialysis patients. Am J Nephrol 30:389–398CrossRefPubMed
3.
Zurück zum Zitat Wetmore JB, Lovett DH, Hung AM, Cook-Wiens G, Mahnken JD, Sen S, Johansen KL (2008) Associations of interleukin-6, C-reactive protein and serum amyloid A with mortality in haemodialysis patients. Nephrology 13:593–600PubMedCentralCrossRefPubMed Wetmore JB, Lovett DH, Hung AM, Cook-Wiens G, Mahnken JD, Sen S, Johansen KL (2008) Associations of interleukin-6, C-reactive protein and serum amyloid A with mortality in haemodialysis patients. Nephrology 13:593–600PubMedCentralCrossRefPubMed
4.
Zurück zum Zitat Honda H, Qureshi AR, Heimburger O, Barany P, Wang K, Pecoits-Filho R, Stenvinkel P, Lindholm B (2006) Serum albumin, C-reactive protein, interleukin 6, and fetuin A as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis 47:139–148CrossRefPubMed Honda H, Qureshi AR, Heimburger O, Barany P, Wang K, Pecoits-Filho R, Stenvinkel P, Lindholm B (2006) Serum albumin, C-reactive protein, interleukin 6, and fetuin A as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis 47:139–148CrossRefPubMed
5.
Zurück zum Zitat Sonikian M, Metaxaki P, Papavasileiou D, Boufidou F, Nikolaou C, Vlassopoulos D, Vlahakos DV (2010) Effects of interleukin-6 on depression risk in dialysis patients. Am J Nephrol 31:303–308CrossRefPubMed Sonikian M, Metaxaki P, Papavasileiou D, Boufidou F, Nikolaou C, Vlassopoulos D, Vlahakos DV (2010) Effects of interleukin-6 on depression risk in dialysis patients. Am J Nephrol 31:303–308CrossRefPubMed
6.
Zurück zum Zitat Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) The effect of novel polymorphisms in the interleukin-6 gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376PubMedCentralCrossRefPubMed Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) The effect of novel polymorphisms in the interleukin-6 gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376PubMedCentralCrossRefPubMed
7.
Zurück zum Zitat Mittal RD, Manchanda PK (2007) Association of interleukin (IL)-4 intron-3 and IL-6-174 G/C gene polymorphism with susceptibility to end-stage renal disease. Immunogenetics 59:159–165CrossRefPubMed Mittal RD, Manchanda PK (2007) Association of interleukin (IL)-4 intron-3 and IL-6-174 G/C gene polymorphism with susceptibility to end-stage renal disease. Immunogenetics 59:159–165CrossRefPubMed
8.
Zurück zum Zitat Buraczynska M, Jozwiak L, Ksiazek P, Borowicz E, Mierzicki P (2007) Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis. Trans Res 150:101–105CrossRef Buraczynska M, Jozwiak L, Ksiazek P, Borowicz E, Mierzicki P (2007) Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis. Trans Res 150:101–105CrossRef
9.
Zurück zum Zitat Balding J, Healy CM, Livingstone WJ, White B, Mynett-Johnson L, Cafferkey M, Smith OP (2003) Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease? Genes Immun 4:533–540CrossRefPubMed Balding J, Healy CM, Livingstone WJ, White B, Mynett-Johnson L, Cafferkey M, Smith OP (2003) Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease? Genes Immun 4:533–540CrossRefPubMed
10.
Zurück zum Zitat Schluter B, Raufhake C, Erren M, Erren M, Schotte H, Kipp F, Rust S, Van Aken H, Assmann G, Berendes E (2002) Effect of the interleukin-6 promoter polymorphism (−174 G/C) on the incidence and outcome of sepsis. Crit Care Med 30:32–37CrossRefPubMed Schluter B, Raufhake C, Erren M, Erren M, Schotte H, Kipp F, Rust S, Van Aken H, Assmann G, Berendes E (2002) Effect of the interleukin-6 promoter polymorphism (−174 G/C) on the incidence and outcome of sepsis. Crit Care Med 30:32–37CrossRefPubMed
11.
Zurück zum Zitat Martin-Loeches I, Sole-Violan J, Rodriguez de Castro F, García-Laorden MI, Borderías L, Blanquer J, Rajas O, Briones ML, Aspa J, Herrera-Ramos E, Marcos-Ramos JA, Sologuren I, González-Quevedo N, Ferrer-Agüero JM, Noda J, Rodríguez-Gallego C (2012) Variants at the promoter of interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia. Intensive Care Med 38:256–262CrossRefPubMed Martin-Loeches I, Sole-Violan J, Rodriguez de Castro F, García-Laorden MI, Borderías L, Blanquer J, Rajas O, Briones ML, Aspa J, Herrera-Ramos E, Marcos-Ramos JA, Sologuren I, González-Quevedo N, Ferrer-Agüero JM, Noda J, Rodríguez-Gallego C (2012) Variants at the promoter of interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia. Intensive Care Med 38:256–262CrossRefPubMed
12.
Zurück zum Zitat Okada R, Wakai K, Naito M (2012) Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study. BMC Nephrol 13:2PubMedCentralCrossRefPubMed Okada R, Wakai K, Naito M (2012) Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study. BMC Nephrol 13:2PubMedCentralCrossRefPubMed
13.
Zurück zum Zitat Calandra T, Cohen J (2005) The international sepsis forum consensus definitions of infections in the intensive care unit. Crit Care Med 33:1639–1648CrossRef Calandra T, Cohen J (2005) The international sepsis forum consensus definitions of infections in the intensive care unit. Crit Care Med 33:1639–1648CrossRef
14.
Zurück zum Zitat Scrutinio D, Passantino A, Santoro D, Cacciapaglia E, Farinola G (2009) Prognostic value of formulas estimating excretory renal function in the elderly with systolic heart failure. Age Ageing 38:296–301CrossRefPubMed Scrutinio D, Passantino A, Santoro D, Cacciapaglia E, Farinola G (2009) Prognostic value of formulas estimating excretory renal function in the elderly with systolic heart failure. Age Ageing 38:296–301CrossRefPubMed
15.
Zurück zum Zitat Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256CrossRefPubMed Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256CrossRefPubMed
16.
Zurück zum Zitat Yalçin S, Kayalti Z, Söylemezoğlu T (2011) Role of interleukin-6 -176G/C promoter polymorphism in trace metal levels of autopsy kidney and liver tissues. Int J Hyg Envir Health 214:219–224CrossRef Yalçin S, Kayalti Z, Söylemezoğlu T (2011) Role of interleukin-6 -176G/C promoter polymorphism in trace metal levels of autopsy kidney and liver tissues. Int J Hyg Envir Health 214:219–224CrossRef
17.
Zurück zum Zitat Yalcin S, Demirbas S, Onguru O (2012) Interleukin-6 (−174G/C) promoter polymorphism in patients infected by hepatitis B virus. J Exp Inter Med 2:173–177 Yalcin S, Demirbas S, Onguru O (2012) Interleukin-6 (−174G/C) promoter polymorphism in patients infected by hepatitis B virus. J Exp Inter Med 2:173–177
18.
Zurück zum Zitat Zavaleta-Muñiz SA, Martín-Márquez BT, Gonzalez-Lopez L et al. (2013) The -174G/C and -572G/C interleukin 6 promoter gene polymorphisms in Mexican patients with rheumatoid arthritis: a case–control study. Clin Develop Immunol 2013:959084 Zavaleta-Muñiz SA, Martín-Márquez BT, Gonzalez-Lopez L et al. (2013) The -174G/C and -572G/C interleukin 6 promoter gene polymorphisms in Mexican patients with rheumatoid arthritis: a case–control study. Clin Develop Immunol 2013:959084
19.
Zurück zum Zitat Cussigh A, Falleti E, Fabris C, Gonzalez-Montoya NG, Díaz-Toscano ML, Ponce-Guarneros JM, Ruiz-Padilla AJ, Vázquez-Del Mercado M, Maldonado-González M, Fafutis-Morris M, Flores-Martínez SE, Martínez-García EA, Gamez-Nava JI (2011) Interleukin promoter polymorphisms influence the outcome of chronic hepatitis C. Immunogenetics 63:33–41CrossRefPubMed Cussigh A, Falleti E, Fabris C, Gonzalez-Montoya NG, Díaz-Toscano ML, Ponce-Guarneros JM, Ruiz-Padilla AJ, Vázquez-Del Mercado M, Maldonado-González M, Fafutis-Morris M, Flores-Martínez SE, Martínez-García EA, Gamez-Nava JI (2011) Interleukin promoter polymorphisms influence the outcome of chronic hepatitis C. Immunogenetics 63:33–41CrossRefPubMed
20.
Zurück zum Zitat Falleti E, Fabris C, Vandelli C, Colletta C, Cussigh A, Smirne C, Fontanini E, Cmet S, Minisini R, Bitetto D, Toniutto P, Pirisi M (2010) Genetic polymorphisms of interleukin-6 modulate fibrosis progression in mild chronic hepatitis C. Hum Immunol 71:999–1004CrossRefPubMed Falleti E, Fabris C, Vandelli C, Colletta C, Cussigh A, Smirne C, Fontanini E, Cmet S, Minisini R, Bitetto D, Toniutto P, Pirisi M (2010) Genetic polymorphisms of interleukin-6 modulate fibrosis progression in mild chronic hepatitis C. Hum Immunol 71:999–1004CrossRefPubMed
21.
Zurück zum Zitat Yee LJ, Im K, Borg B, Yang H, Liang TJ (2009) Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection. Genes Immun 10:365–372PubMedCentralCrossRefPubMed Yee LJ, Im K, Borg B, Yang H, Liang TJ (2009) Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection. Genes Immun 10:365–372PubMedCentralCrossRefPubMed
22.
Zurück zum Zitat Michalek J, Svetlikova P, Fedora M, Klimovic M, Klapacova L, Bartosova D, Hrstkova H, Hubacek JA (2007) Interleukin-6 gene variants and the risk of sepsis development in children. Hum Immunol 68:756–760CrossRefPubMed Michalek J, Svetlikova P, Fedora M, Klimovic M, Klapacova L, Bartosova D, Hrstkova H, Hubacek JA (2007) Interleukin-6 gene variants and the risk of sepsis development in children. Hum Immunol 68:756–760CrossRefPubMed
23.
Zurück zum Zitat Schaaf B, Rupp J, Muller-Steinhardt M, Kruse J (2005) The interleukin-6 -174 promoter polymorphism is associated with extrapulmonary bacterial dissemination in Streptococcus pneumoniae infection. Cytokine 31:324–328CrossRefPubMed Schaaf B, Rupp J, Muller-Steinhardt M, Kruse J (2005) The interleukin-6 -174 promoter polymorphism is associated with extrapulmonary bacterial dissemination in Streptococcus pneumoniae infection. Cytokine 31:324–328CrossRefPubMed
24.
Zurück zum Zitat Sutherland AM, Walley KR, Manocha S, Rusell JA (2005) The association of interleukin 6 haplotype clades with mortality in critically ill adults. Arch Intern Med 165:75–82CrossRefPubMed Sutherland AM, Walley KR, Manocha S, Rusell JA (2005) The association of interleukin 6 haplotype clades with mortality in critically ill adults. Arch Intern Med 165:75–82CrossRefPubMed
25.
Zurück zum Zitat Sarnak MJ, Jaber BL (2000) Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int 58:1758–1764CrossRefPubMed Sarnak MJ, Jaber BL (2000) Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int 58:1758–1764CrossRefPubMed
Metadaten
Titel
-572 G/C single nucleotide polymorphism of interleukin-6 and sepsis predisposition in chronic renal disease
verfasst von
A. Panayides
A. Ioakeimidou
V. Karamouzos
N. Antonakos
I. Koutelidakis
G. Giannikopoulos
K. Makaritsis
N. Voloudakis
K. Toutouzas
N. Rovina
M. Bristianou
G. Damoraki
C. Routsi
E. J. Giamarellos-Bourboulis
on behalf of the Hellenic Sepsis Study Group
Publikationsdatum
01.12.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 12/2015
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-015-2500-0

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