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Clinical Immunology |
1 Department of Medicine, Danderyd University Hospital, Stockholm, Sweden.
Departments of2
Cardiology and 3
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, and 4
Department of Clinical Chemistry, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
5 Department of Cardiovascular Medicine, University of Oxford and Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
aAddress correspondence to this author at: Department of Medicine, Danderyd University Hospital, SE-182 88 Stockholm, Sweden. Fax 46-8-622-68-10; e-mail marie.bennermo{at}ds.se.
Background: A single-nucleotide polymorphism (SNP) in the promoter region of the interleukin-6 (IL-6) gene at position –174 (G>C) has been reported to be associated with a variety of major diseases, such as Alzheimer disease, atherosclerosis, and cardiovascular disease, cancer, non-insulin-dependent diabetes mellitus, osteoporosis, sepsis, and systemic-onset juvenile chronic arthritis. However, authors of previous in vitro and in vivo studies have reported conflicting results regarding the functionality of this polymorphism. We therefore aimed to clarify the role of the –174 SNP for the induction of IL-6 in vivo.
Methods: We vaccinated 20 and 18 healthy individuals homozygous for the –174 C and G alleles, respectively, with 1 mL of Salmonella typhii vaccine. IL-1ß, IL-6, and tumor necrosis factor-
(TNF-) were measured in the blood at baseline and up to 24 h after vaccination.
Results: Individuals with the G genotype had significantly higher plasma IL-6 values at 6, 8, and 10 h after vaccination than did individuals with the C genotype (P <0.005). There were no differences between the two genotypes regarding serum concentrations of IL-1ß and TNF- before or after vaccination.
Conclusions: The –174 G>C SNP in the promoter region of the IL-6 gene is functional in vivo with an increased inflammatory response associated with the G allele. Considering the central role of IL-6 in a variety of major diseases, the present finding might be of major relevance.
The following articles in journals at HighWire Press have cited this article:
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  B Resch, A Radinger, C Mannhalter, A Binder, J Haas, and W D Muller Interleukin-6 G(-174)C polymorphism is associated with mental retardation in cystic periventricular leucomalacia in preterm infants Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2009; 94(4): F304 - F306. [Abstract] [Full Text] [PDF]
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 W.-C. Liao, J.-T. Lin, C.-Y. Wu, S.-P. Huang, M.-T. Lin, A. S.-H. Wu, Y.-J. Huang, and M.-S. Wu Serum Interleukin-6 Level but not Genotype Predicts Survival after Resection in Stages II and III Gastric Carcinoma Clin. Cancer Res., January 15, 2008; 14(2): 428 - 434. [Abstract] [Full Text] [PDF]
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 A. K. Sasser, N. J. Sullivan, A. W. Studebaker, L. F. Hendey, A. E. Axel, and B. M. Hall Interleukin-6 is a potent growth factor for ER-{alpha}-positive human breast cancer FASEB J, November 1, 2007; 21(13): 3763 - 3770. [Abstract] [Full Text] [PDF]
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 L. Qi, C. Zhang, R. M. van Dam, and F. B. Hu Interleukin-6 Genetic Variability and Adiposity: Associations in Two Prospective Cohorts and Systematic Review in 26,944 Individuals J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3618 - 3625. [Abstract] [Full Text] [PDF]
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 M. L. Slattery, K. Curtin, R. Baumgartner, C. Sweeney, T. Byers, A. R. Giuliano, K. B. Baumgartner, and R. R. Wolff IL6, Aspirin, Nonsteroidal Anti-inflammatory Drugs, and Breast Cancer Risk in Women Living in the Southwestern United States Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 747 - 755. [Abstract] [Full Text] [PDF]
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 C. Winkelman, P. A. Higgins, Y. J. K. Chen, and A. D. Levine Cytokines in Chronically Critically Ill Patients After Activity and Rest Biol Res Nurs, April 1, 2007; 8(4): 261 - 271. [Abstract] [PDF]
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 R. B. Yates and M. Stafford-Smith The genetic determinants of renal impairment following cardiac surgery. Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2006; 10(4): 314 - 326. [Abstract] [PDF]
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 C. Huth, I. M. Heid, C. Vollmert, C. Gieger, H. Grallert, J. K. Wolford, B. Langer, B. Thorand, N. Klopp, Y. H. Hamid, et al. IL6 Gene Promoter Polymorphisms and Type 2 Diabetes: Joint Analysis of Individual Participants' Data From 21 Studies. Diabetes, October 1, 2006; 55(10): 2915 - 2921. [Abstract] [Full Text] [PDF]
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 I. Wernstedt, A. Edgley, A. Berndtsson, J. Faldt, G. Bergstrom, V. Wallenius, and J.-O. Jansson Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R551 - R557. [Abstract] [Full Text] [PDF]
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 L. Qi, R. M. van Dam, J. B. Meigs, J. E. Manson, D. Hunter, and F. B. Hu Genetic variation in IL6 gene and type 2 diabetes: tagging-SNP haplotype analysis in large-scale case-control study and meta-analysis Hum. Mol. Genet., June 1, 2006; 15(11): 1914 - 1920. [Abstract] [Full Text] [PDF]
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 A. Seow, D. P. Ng, S. Choo, P. Eng, W.-T. Poh, T. Ming, and Y.-T. Wang Joint effect of asthma/atopy and an IL-6 gene polymorphism on lung cancer risk among lifetime non-smoking Chinese women Carcinogenesis, June 1, 2006; 27(6): 1240 - 1244. [Abstract] [Full Text] [PDF]
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L. B. Sansbury, A. W. Bergen, K. L. Wanke, B. Yu, N. E. Caporaso, N. Chatterjee, L. Ratnasinghe, A. Schatzkin, T. A. Lehman, A. Kalidindi, et al. Inflammatory cytokine gene polymorphisms, nonsteroidal anti-inflammatory drug use, and risk of adenoma polyp recurrence in the polyp prevention trial. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 494 - 501. [Abstract] [Full Text] [PDF]
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 C. Grimm, L. Six, C. Tomovski, P. Speiser, E. Joura, R. Zeillinger, G. Sliutz, A. Reinthaller, and L. A. Hefler A Common Interleukin-6 Promoter Polymorphism in Patients With Vulvar Cancer Reproductive Sciences, December 1, 2005; 12(8): 617 - 620. [Abstract] [PDF]
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O. P. Kristiansen and T. Mandrup-Poulsen Interleukin-6 and Diabetes: The Good, the Bad, or the Indifferent? Diabetes, December 1, 2005; 54(suppl_2): S114 - S124. [Abstract] [Full Text] [PDF]
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E. Corpeleijn, W. H. M. Saris, E. H. J. M. Jansen, P. M. H. J. Roekaerts, E. J. M. Feskens, and E. E. Blaak Postprandial Interleukin-6 Release from Skeletal Muscle in Men with Impaired Glucose Tolerance Can Be Reduced by Weight Loss J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5819 - 5824. [Abstract] [Full Text] [PDF]
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 K. Oen, P. N. Malleson, D. A. Cabral, A. M. Rosenberg, R. E. Petty, P. Nickerson, and M. Reed Cytokine genotypes correlate with pain and radiologically defined joint damage in patients with juvenile rheumatoid arthritis Rheumatology, September 1, 2005; 44(9): 1115 - 1121. [Abstract] [Full Text] [PDF]
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 J. P. Liuzzi, L. A. Lichten, S. Rivera, R. K. Blanchard, T. B. Aydemir, M. D. Knutson, T. Ganz, and R. J. Cousins Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response PNAS, May 10, 2005; 102(19): 6843 - 6848. [Abstract] [Full Text] [PDF]
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