Abstract
The relationship of TNF-α promoter polymorphisms and ankylosing spondylitis (AS) has been reported with conflicting results. We perform this meta-analysis to collect all the relevant studies up to date to further clarify the association of TNF-α promoter polymorphisms with AS. A review was conducted of studies reporting on the association between TNF-α promoter polymorphisms and AS susceptibility in Medline, Pubmed, Embase, and Web of Science. The numbers of individuals with various genotypes and alleles in both the case and control groups were extracted from relevant studies. Odds ratios (ORs) with 95% confidence interval (CI) were used to estimate the association. Fourteen eligible studies, contributing data on 3,880 subjects (1,766 patients; 2,114 controls), were included in this meta-analysis. The ORs of various comparisons indicated that there was no association between TNF-α 238, 308 polymorphisms, and AS susceptibility in the overall population. For HLA-B27+ population, although the frequency of 308 A allele decreased in AS patients (OR = 0.721; 95%CI = 0.522–0.995), the result was no longer statistically significant after excluding the Hardy–Weinberg equilibrium violation studies (OR = 1.150; 95%CI = 0.568–2.310). No relationship was found between TNF-α promoter 238 polymorphisms and AS in HLA-b27+ population. No association was found between TNF-α promoter 238/308 polymorphisms and ankylosing spondylitis susceptibility in both the overall and HLA-B27+ population.
Similar content being viewed by others
References
Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD (1973) Ankylosing spondylitis and HL-A 27. Lancet 1:904–907
Khan MA, Ball EJ (2002) Genetic aspects of ankylosing spondylitis. Best Pract Res Clin Rheumatol 16:675–690
Rubin LA, Amos CI, Wade JA et al (1994) Investigating the genetic basis for ankylosing spondylitis. Linkage studies with the major histocompatibility complex region. Arthritis Rheum 37:1212–1220
van der Linden SM, Valkenburg HA, de Jongh BM, Cats A (1984) The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum 27:241–249
Benjamin R, Parham P (1990) Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol Today 11:137–142
Tracey KJ, Cerami A (1993) Tumor necrosis factor: an updated review of its biology. Crit Care Med 21:S415–S422
Glossop JR, Nixon NB, Dawes PT, Hassell AB, Mattey DL (2003) No association of polymorphisms in the tumor necrosis factor receptor I and receptor II genes with disease severity in rheumatoid arthritis. J Rheumatol 30:1406–1409
Wilson AG, de Vries N, Pociot F, di Giovine FS, van der Putte LB, Duff GW (1993) An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA a1, B8, and DR3 alleles. J Exp Med 177:557–560
D'Alfonso S, Richiardi PM (1994) A polymorphic variation in a putative regulation box of the TNFa promoter region. Immunogenetics 39:150–154
Lee YH, Song GG (2009) Lack of association of TNF-alpha promoter polymorphisms with ankylosing spondylitis: a meta-analysis. Rheumatology (Oxford) 48:1359–1362
Chatzikyriakidou A, Georgiou I, Voulgari PV, Drosos AA (2009) The role of tumor necrosis factor (TNF)-alpha and TNF receptor polymorphisms in susceptibility to ankylosing spondylitis. Clin Exp Rheumatol 27:645–648
Lu MC, Yang KL, Tung CH et al (2008) Higher LPS-stimulated TNF-alpha mRNA levels in peripheral blood mononuclear cells from Chinese ankylosing spondylitis patients with −308G/A polymorphism in promoter region of tumor necrosis factor: association with distinct A33/B58/Cw10 haplotypes. Rheumatol Int 29:189–195
Nicknam MH, Mahmoudi M, Amirzargar AA, Jamshidi AR, Rezaei N, Nikbin B (2009) HLA-B27 subtypes and tumor necrosis factor alpha promoter region polymorphism in Iranian patients with ankylosing spondylitis. Eur Cytokine Netw 20:17–20
Shiau MY, Lo MK, Chang CP, Yang TP, Ho KT, Chang YH (2007) Association of tumour necrosis factor alpha promoter polymorphisms with ankylosing spondylitis in Taiwan. Ann Rheum Dis 66:562–563
Sousa E, Caetano-Lopes J, Pinto P et al (2009) Ankylosing spondylitis susceptibility and severity—contribution of TNF gene promoter polymorphisms at positions −238 and −308. Ann N Y Acad Sci 1173:581–588
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560
Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
Aguillon JC, Cruzat A, Aravena O, Salazar L, Llanos C, Cuchacovich M (2006) Could single-nucleotide polymorphisms (SNPs) affecting the tumour necrosis factor promoter be considered as part of rheumatoid arthritis evolution? Immunobiology 211:75–84
De Vos M (2004) Review article: joint involvement in inflammatory bowel disease. Aliment Pharmacol Ther 20(Suppl 4):36–42
Rudwaleit M, Hohler T (2001) Cytokine gene polymorphisms relevant for the spondyloarthropathies. Curr Opin Rheumatol 13:250–254
Field M (2001) Tumour necrosis factor polymorphisms in rheumatic diseases. QJM 94:237–246
Seitz M, Wirthmuller U, Moller B, Villiger PM (2007) The −308 tumour necrosis factor-alpha gene polymorphism predicts therapeutic response to TNFalpha-blockers in rheumatoid arthritis and spondyloarthritis patients. Rheumatology (Oxford) 46:93–96
Fraile A, Nieto A, Beraun Y, Vinasco J, Mataran L, Martin J (1998) Tumor necrosis factor gene polymorphisms in ankylosing spondylitis. Tissue Antigens 51:386–390
Gonzalez S, Torre-Alonso JC, Martinez-Borra J et al (2001) TNF-238a promoter polymorphism contributes to susceptibility to ankylosing spondylitis in HLA-B27 negative patients. J Rheumatol 28:1288–1293
Hohler T, Schaper T, Schneider PM, Meyer ZBK, Marker-Hermann E (1998) Association of different tumor necrosis factor alpha promoter allele frequencies with ankylosing spondylitis in HLA-B27 positive individuals. Arthritis Rheum 41:1489–1492
Kaijzel EL, Brinkman BM, van Krugten MV et al (1999) Polymorphism within the tumor necrosis factor alpha (TNF) promoter region in patients with ankylosing spondylitis. Hum Immunol 60:140–144
Martinez-Borra J, Gonzalez S, Lopez-Vazquez A et al (2000) HLA-B27 alone rather than B27-related class I haplotypes contributes to ankylosing spondylitis susceptibility. Hum Immunol 61:131–139
McGarry F, Walker R, Sturrock R, Field M (1999) The −308.1 polymorphism in the promoter region of the tumor necrosis factor gene is associated with ankylosing spondylitis independent of HLA-B27. J Rheumatol 26:1110–1116
Milicic A, Lindheimer F, Laval S et al (2000) Interethnic studies of tnf polymorphisms confirm the likely presence of a second mhc susceptibility locus in ankylosing spondylitis. Genes Immun 1:418–422
Vargas-Alarcon G, Casasola-Vargas J, Rodriguez-Perez JM et al (2006) Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with spondyloarthritis. Hum Immunol 67:826–832
Verjans GM, Brinkman BM, Van Doornik CE, Kijlstra A, Verweij CL (1994) Polymorphism of tumour necrosis factor-alpha (TNF-alpha) at position −308 in relation to ankylosing spondylitis. Clin Exp Immunol 97:45–47
van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis, A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368
Moll JM, Wright V (1973) New York clinical criteria for ankylosing spondylitis. A statistical evaluation. Ann Rheum Dis 32:354–363
Reveille JD (1993) The interplay of nature versus nurture in predisposition to the rheumatic diseases. Rheum Dis Clin North Am 19:15–27
Pei J, Choo SY, Spies T, Strominger JL, Hansen JA (1991) Association of four HLA class III region genomic markers with HLA haplotypes. Tissue Antigens 37:191–196
Trikalinos TA, Salanti G, Khoury MJ, Ioannidis JP (2006) Impact of violations and deviations in Hardy–Weinberg equilibrium on postulated gene–disease associations. Am J Epidemiol 163:300–309
Goie TH, Steven MM, van der Linden SM, Cats A (1985) Evaluation of diagnostic criteria for ankylosing spondylitis: a comparison of the Rome, New York and modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis. Br J Rheumatol 24:242–249
Disclosures
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, B., Wang, P. & Li, H. The association between TNF-α promoter polymorphisms and ankylosing spondylitis: a meta-analysis. Clin Rheumatol 29, 983–990 (2010). https://doi.org/10.1007/s10067-010-1499-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-010-1499-y