Cell Biochem Biophys DOI 10.1007/s12013-014-9905-8
LETTER TO THE EDITOR
Tumor Necrosis Factor (TNF)-alpha Promoter Polymorphisms in Ankylosing Spondylitis: Comment on the Article by Ji et al Zhongwen Chen • Rui Ge
Ó Springer Science+Business Media New York 2014
Abstract TNF-a promoter polymorphisms may be associated with the severity rather than the susceptibility of AS. Further studies with a large sample size and precise methodology are needed. Interactions may already exist between gene and environment. All of these are helpful to determine the exact mechanisms of TNF-a promoter polymorphisms in AS. Keywords Tumor necrosis factor alpha Ankylosing spondylitis Polymorphisms
To the Editor, Tumor necrosis factor alpha (TNF-a), as a macrophagederived proinflammatory cytokine, has been recently implicated in the pathogenesis in some inflammatory diseases due to its ability to modify cytokine levels and clinical outcomes. The relationship between TNF-a promoter polymorphisms and ankylosing spondylitis (AS) has been reported in many studies. Recently, Ji et al. [1] reported that there was no association between TNF-a promoter polymorphisms and AS. However, the existing data seem to be controversial. A meta-analysis, which including 14 case–control studies, showed that TNF-a promoter polymorphisms could have a small influence on AS susceptibility [2]. Inconsistently, some studies demonstrated that no association was found between TNF-a promoter 238/308 polymorphisms and AS susceptibility in both the overall and HLA-B27?population. Z. Chen R. Ge (&) Jiaxing Center for Disease Control and Prevention, No. 486, Wen Qiao Road, Jiaxing 314050, Zhejiang, China e-mail: [email protected]
Subgroup analysis by ethnicity and HLA-B27 positivity did not change the results [3, 4]. This inconsistency may be partly attributed to the different models used and sample sizes. Furthermore, study on the TNF-a promoter 238/308 polymorphisms in spondyloarthritis (SpAs) patients had shown that the differences between uSpA, ReA, and healthy subjects (HS) were significant. These differences were not found in AS. By contrast, significant differences were observed when compared to the serum TNF-a level between patients with SpAs and its subtypes and HS [5]. TNF-a protein is a potent proinflammatory cytokine and immune modulator of joint destruction. Poddubnyy et al. [6] reported the percentage of TNF-a-producing CD8?T cells in HLA-B27 positive AS patients is significantly lower than in negative ones. The A allele of TNF-a promoter 308 was associated with a lower percentage of TNFa-producing CD4?T cells. But there was no significant correlation between clinical or radiological measurements and TNF-a promoter polymorphisms. Consequently, we conclude that TNF-a promoter polymorphisms may be associated with the severity rather than the susceptibility of AS. Further studies with a large sample size and precise methodology are needed. Interactions may already exist between gene and environment. All of these are helpful to determine the exact mechanisms of TNF-a promoter polymorphisms in AS.
References 1. Ji, Y., Yang, X., Yang, L., et al. (2013). Studies on correlation between single-nucleotide polymorphisms of tumor necrosis factor gene and different stages of ankylosing spondylitis. Cell Biochemistry and Biophysics, 67(3), 915–922. doi:10.1007/s12013-0139582-z.
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Cell Biochem Biophys 2. Ma, B., Wang, J., Ren, X., et al. (2013). The association between tumor necrosis factor alpha promoter polymorphisms and ankylosing spondylitis: A meta-analysis. Human Immunology, 74(10), 1357–1362. doi:10.1016/j.humimm.2013.06.037. 3. Li, B., Wang, P., & Li, H. (2010). The association between TNFalpha promoter polymorphisms and ankylosing spondylitis: a meta-analysis. Clinical Rheumatology, 29(9), 983–990. 4. Lee, Y. H., & Song, G. G. (2009). Lack of association of TNFalpha promoter polymorphisms with ankylosing spondylitis: a meta-analysis. Rheumatology, 48(11), 1359–1362. 5. Romero-Sa´nchez, C., London˜o, J., Delgado, G., et al. (2012). Association of tumor necrosis factor alpha-308 promoter
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polymorphism with spondyloarthritis patients in Colombia. Rheumatology International, 32(7), 2195–2197. 6. Poddubnyy, D. A., Ma¨rker-Hermann, E., Kaluza-Schilling, W., et al. (2011). Relation of HLA-B27, tumor necrosis factor-a promoter gene polymorphisms, and T cell cytokine production in ankylosing spondylitis—a comprehensive genotype-phenotype analysis from an observational cohort. Journal of Rheumatology, 38(11), 2436–2441. doi:10.3899/jrheum.110130.
LETTER TO THE EDITOR
Tumor Necrosis Factor (TNF)-alpha Promoter Polymorphisms in Ankylosing Spondylitis: Comment on the Article by Ji et al Zhongwen Chen • Rui Ge
Ó Springer Science+Business Media New York 2014
Abstract TNF-a promoter polymorphisms may be associated with the severity rather than the susceptibility of AS. Further studies with a large sample size and precise methodology are needed. Interactions may already exist between gene and environment. All of these are helpful to determine the exact mechanisms of TNF-a promoter polymorphisms in AS. Keywords Tumor necrosis factor alpha Ankylosing spondylitis Polymorphisms
To the Editor, Tumor necrosis factor alpha (TNF-a), as a macrophagederived proinflammatory cytokine, has been recently implicated in the pathogenesis in some inflammatory diseases due to its ability to modify cytokine levels and clinical outcomes. The relationship between TNF-a promoter polymorphisms and ankylosing spondylitis (AS) has been reported in many studies. Recently, Ji et al. [1] reported that there was no association between TNF-a promoter polymorphisms and AS. However, the existing data seem to be controversial. A meta-analysis, which including 14 case–control studies, showed that TNF-a promoter polymorphisms could have a small influence on AS susceptibility [2]. Inconsistently, some studies demonstrated that no association was found between TNF-a promoter 238/308 polymorphisms and AS susceptibility in both the overall and HLA-B27?population. Z. Chen R. Ge (&) Jiaxing Center for Disease Control and Prevention, No. 486, Wen Qiao Road, Jiaxing 314050, Zhejiang, China e-mail: [email protected]
Subgroup analysis by ethnicity and HLA-B27 positivity did not change the results [3, 4]. This inconsistency may be partly attributed to the different models used and sample sizes. Furthermore, study on the TNF-a promoter 238/308 polymorphisms in spondyloarthritis (SpAs) patients had shown that the differences between uSpA, ReA, and healthy subjects (HS) were significant. These differences were not found in AS. By contrast, significant differences were observed when compared to the serum TNF-a level between patients with SpAs and its subtypes and HS [5]. TNF-a protein is a potent proinflammatory cytokine and immune modulator of joint destruction. Poddubnyy et al. [6] reported the percentage of TNF-a-producing CD8?T cells in HLA-B27 positive AS patients is significantly lower than in negative ones. The A allele of TNF-a promoter 308 was associated with a lower percentage of TNFa-producing CD4?T cells. But there was no significant correlation between clinical or radiological measurements and TNF-a promoter polymorphisms. Consequently, we conclude that TNF-a promoter polymorphisms may be associated with the severity rather than the susceptibility of AS. Further studies with a large sample size and precise methodology are needed. Interactions may already exist between gene and environment. All of these are helpful to determine the exact mechanisms of TNF-a promoter polymorphisms in AS.
References 1. Ji, Y., Yang, X., Yang, L., et al. (2013). Studies on correlation between single-nucleotide polymorphisms of tumor necrosis factor gene and different stages of ankylosing spondylitis. Cell Biochemistry and Biophysics, 67(3), 915–922. doi:10.1007/s12013-0139582-z.
123
Cell Biochem Biophys 2. Ma, B., Wang, J., Ren, X., et al. (2013). The association between tumor necrosis factor alpha promoter polymorphisms and ankylosing spondylitis: A meta-analysis. Human Immunology, 74(10), 1357–1362. doi:10.1016/j.humimm.2013.06.037. 3. Li, B., Wang, P., & Li, H. (2010). The association between TNFalpha promoter polymorphisms and ankylosing spondylitis: a meta-analysis. Clinical Rheumatology, 29(9), 983–990. 4. Lee, Y. H., & Song, G. G. (2009). Lack of association of TNFalpha promoter polymorphisms with ankylosing spondylitis: a meta-analysis. Rheumatology, 48(11), 1359–1362. 5. Romero-Sa´nchez, C., London˜o, J., Delgado, G., et al. (2012). Association of tumor necrosis factor alpha-308 promoter
123
polymorphism with spondyloarthritis patients in Colombia. Rheumatology International, 32(7), 2195–2197. 6. Poddubnyy, D. A., Ma¨rker-Hermann, E., Kaluza-Schilling, W., et al. (2011). Relation of HLA-B27, tumor necrosis factor-a promoter gene polymorphisms, and T cell cytokine production in ankylosing spondylitis—a comprehensive genotype-phenotype analysis from an observational cohort. Journal of Rheumatology, 38(11), 2436–2441. doi:10.3899/jrheum.110130.
