Skip to main content
Erschienen in: Rheumatology International 1/2009

01.11.2009 | Original Article

IkBα promoter polymorphisms in patients with ankylosing spondylitis

verfasst von: Yu-Hung Hung, Tsan-Teng Ou, Chia-Hui Lin, Ruei-Nian Li, Yu-Chih Lin, Wen-Chan Tsai, Hong-Wen Liu, Jeng-Hsien Yen

Erschienen in: Rheumatology International | Ausgabe 1/2009

Einloggen, um Zugang zu erhalten

Abstract

The purpose of this study is to investigate the association of IκBα with the development of ankylosing spondylitis (AS) in Taiwan. One hundred and fifty-four patients with AS and 112 unrelated healthy controls were enrolled in this study. The IκBα-881A/G, -826C/T, -550A/T, -519C/T, and -297C/T polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism method. This study demonstrated that the genotype frequencies of IκBα-826C/T and -826T/T, and allele frequencies of IκBα-826T were significantly higher in the patients with AS than in the controls. We also found that the estimated haplotype frequencies of IκBα-881A -826T -550A -519C -297C and IκBα-881A -826C -550A -519T -297C were significantly increased in the patient with AS in comparison with that of the controls. In contrast, the estimated haplotype frequency of IκBα-881A -826C -550A -519C -297C was significantly decreased in the patients with AS. This study demonstrates that IκBα-826T is associated with the development of AS. Furthermore, the IκBα-881A -826T -550A -519C -297C and IκBα-881A -826C -550A -519T -297C haplotypes are related to susceptibility to AS in Taiwan.
Literatur
2.
Zurück zum Zitat Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, Shatford JL, Taylor A, Calin A, Wordsworth P (1997) Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum 40:1823–1828. doi:10.1002/art.1780401015 CrossRefPubMed Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, Shatford JL, Taylor A, Calin A, Wordsworth P (1997) Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum 40:1823–1828. doi:10.​1002/​art.​1780401015 CrossRefPubMed
3.
Zurück zum Zitat 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. doi:10.1002/art.1780270301 CrossRefPubMed 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. doi:10.​1002/​art.​1780270301 CrossRefPubMed
5.
Zurück zum Zitat Brown MA (2007) Breakthroughs in genetic studies of ankylosing spondylitis. Rheumatology (Oxford) 47:132–137CrossRef Brown MA (2007) Breakthroughs in genetic studies of ankylosing spondylitis. Rheumatology (Oxford) 47:132–137CrossRef
6.
Zurück zum Zitat Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ et al (2007) Association Scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 39:1329–1337. doi:10.1038/ng.2007.17 CrossRefPubMed Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ et al (2007) Association Scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 39:1329–1337. doi:10.​1038/​ng.​2007.​17 CrossRefPubMed
7.
Zurück zum Zitat Carter KW, Pluzhnikov A, Timms AE, Miceli-Richard C, Bourgain C, Wordsworth BP, Jean-Pierre H, Cox NJ, Palmer LJ, Breban M et al (2007) Combined analysis of three whole genome linkage scans for ankylosing spondylitis. Rheumatology (Oxford) 46:763–771. doi:10.1093/rheumatology/kel443 CrossRef Carter KW, Pluzhnikov A, Timms AE, Miceli-Richard C, Bourgain C, Wordsworth BP, Jean-Pierre H, Cox NJ, Palmer LJ, Breban M et al (2007) Combined analysis of three whole genome linkage scans for ankylosing spondylitis. Rheumatology (Oxford) 46:763–771. doi:10.​1093/​rheumatology/​kel443 CrossRef
8.
Zurück zum Zitat Laval SH, Timms A, Edwards S, Bradbury L, Brophy S, Milicic A, Rubin L, Siminovitch KA, Weeks DE, Calin A et al (2001) Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci. Am J Hum Genet 68:918–926. doi:10.1086/319509 CrossRefPubMed Laval SH, Timms A, Edwards S, Bradbury L, Brophy S, Milicic A, Rubin L, Siminovitch KA, Weeks DE, Calin A et al (2001) Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci. Am J Hum Genet 68:918–926. doi:10.​1086/​319509 CrossRefPubMed
13.
Zurück zum Zitat Castro-Alcaraz S, Miskolci V, Kalasapudi B, Davidson D, Vancurova I (2002) NF-Kappa B regulation in human neutrophils by nuclear I Kappa B alpha: correlation to apoptosis. J Immunol 169:3947–3953PubMed Castro-Alcaraz S, Miskolci V, Kalasapudi B, Davidson D, Vancurova I (2002) NF-Kappa B regulation in human neutrophils by nuclear I Kappa B alpha: correlation to apoptosis. J Immunol 169:3947–3953PubMed
14.
Zurück zum Zitat Campbell IK, Gerondakis S, O’Donnell K, Wicks IP (2000) Distinct roles for the NF-Kappa B1 (P50) and C-Rel transcription factors in inflammatory arthritis. J Clin Invest 105:1799–1806. doi:10.1172/JCI8298 CrossRefPubMed Campbell IK, Gerondakis S, O’Donnell K, Wicks IP (2000) Distinct roles for the NF-Kappa B1 (P50) and C-Rel transcription factors in inflammatory arthritis. J Clin Invest 105:1799–1806. doi:10.​1172/​JCI8298 CrossRefPubMed
17.
Zurück zum Zitat Mozzato-Chamay N, Corbett EL, Bailey RL, Mabey DC, Raynes J, Conway DJ (2001) Polymorphisms in the I kappa B-alpha promoter region and risk of diseases involving inflammation and fibrosis. Genes Immun 2:153–155. doi:10.1038/sj.gene.6363753 CrossRefPubMed Mozzato-Chamay N, Corbett EL, Bailey RL, Mabey DC, Raynes J, Conway DJ (2001) Polymorphisms in the I kappa B-alpha promoter region and risk of diseases involving inflammation and fibrosis. Genes Immun 2:153–155. doi:10.​1038/​sj.​gene.​6363753 CrossRefPubMed
22.
Zurück zum Zitat Arenzana-Seisdedos F, Thompson J, Rodriguez MS, Bachelerie F, Thomas D, Hay RT (1995) Inducible nuclear expression of newly synthesized I Kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-Kappa B. Mol Cell Biol 15:2689–2696PubMed Arenzana-Seisdedos F, Thompson J, Rodriguez MS, Bachelerie F, Thomas D, Hay RT (1995) Inducible nuclear expression of newly synthesized I Kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-Kappa B. Mol Cell Biol 15:2689–2696PubMed
24.
Zurück zum Zitat Arenzana-Seisdedos F, Turpin P, Rodriguez M, Thomas D, Hay RT, Virelizier JL, Dargemont C (1997) Nuclear localization of I Kappa B alpha promotes active transport of NF-Kappa B from the nucleus to the cytoplasm. J Cell Sci 110(Pt 3):369–378PubMed Arenzana-Seisdedos F, Turpin P, Rodriguez M, Thomas D, Hay RT, Virelizier JL, Dargemont C (1997) Nuclear localization of I Kappa B alpha promotes active transport of NF-Kappa B from the nucleus to the cytoplasm. J Cell Sci 110(Pt 3):369–378PubMed
25.
Zurück zum Zitat Ernst MK, Dunn LL, Rice NR (1995) The pest-like sequence of I Kappa B alpha is responsible for inhibition of DNA binding but not for cytoplasmic retention of C-Rel or Rela homodimers. Mol Cell Biol 15:872–882PubMed Ernst MK, Dunn LL, Rice NR (1995) The pest-like sequence of I Kappa B alpha is responsible for inhibition of DNA binding but not for cytoplasmic retention of C-Rel or Rela homodimers. Mol Cell Biol 15:872–882PubMed
26.
Zurück zum Zitat Miterski B, Bohringer S, Klein W, Sindern E, Haupts M, Schimrigk S, Epplen JT (2002) Inhibitors in the NF kappa B cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations. Genes Immun 3:211–219. doi:10.1038/sj.gene.6363846 CrossRefPubMed Miterski B, Bohringer S, Klein W, Sindern E, Haupts M, Schimrigk S, Epplen JT (2002) Inhibitors in the NF kappa B cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations. Genes Immun 3:211–219. doi:10.​1038/​sj.​gene.​6363846 CrossRefPubMed
27.
Zurück zum Zitat Klein W, Tromm A, Folwaczny C, Hagedorn M, Duerig N, Epplen JT, Schmiegel WH, Griga T (2004) A polymorphism of the NFKB IA gene is associated with Crohn’s Disease patients lacking a predisposing allele of the card15 gene. Int J Colorectal Dis 19:153–156. doi:10.1007/s00384-003-0531-y CrossRefPubMed Klein W, Tromm A, Folwaczny C, Hagedorn M, Duerig N, Epplen JT, Schmiegel WH, Griga T (2004) A polymorphism of the NFKB IA gene is associated with Crohn’s Disease patients lacking a predisposing allele of the card15 gene. Int J Colorectal Dis 19:153–156. doi:10.​1007/​s00384-003-0531-y CrossRefPubMed
28.
Zurück zum Zitat Gao J, Pfeifer D, He LJ, Qiao F, Zhang Z, Arbman G, Wang ZL, Jia CR, Carstensen J, Sun XF (2007) Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. Scand J Gastroenterol 42:345–350. doi:10.1080/00365520600880856 CrossRefPubMed Gao J, Pfeifer D, He LJ, Qiao F, Zhang Z, Arbman G, Wang ZL, Jia CR, Carstensen J, Sun XF (2007) Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. Scand J Gastroenterol 42:345–350. doi:10.​1080/​0036552060088085​6 CrossRefPubMed
29.
Zurück zum Zitat Sun XF, Zhang H (2007) Nfkb and Nfkbi polymorphisms in relation to susceptibility of tumour and other diseases. Histol Histopathol 22:1387–1398PubMed Sun XF, Zhang H (2007) Nfkb and Nfkbi polymorphisms in relation to susceptibility of tumour and other diseases. Histol Histopathol 22:1387–1398PubMed
30.
Zurück zum Zitat Abdallah A, Sato H, Grutters JC, Veeraraghavan S, Lympany PA, Ruven HJ, van den Bosch JM, Wells AU, du Bois RM, Welsh KI (2003) Inhibitor Kappa B-Alpha (I Kappa B-alpha) promoter polymorphisms in UK and Dutch sarcoidosis. Genes Immun 4:450–454. doi:10.1038/sj.gene.6364001 CrossRefPubMed Abdallah A, Sato H, Grutters JC, Veeraraghavan S, Lympany PA, Ruven HJ, van den Bosch JM, Wells AU, du Bois RM, Welsh KI (2003) Inhibitor Kappa B-Alpha (I Kappa B-alpha) promoter polymorphisms in UK and Dutch sarcoidosis. Genes Immun 4:450–454. doi:10.​1038/​sj.​gene.​6364001 CrossRefPubMed
31.
Zurück zum Zitat Emmerich F, Meiser M, Hummel M, Demel G, Foss HD, Jundt F, Mathas S, Krappmann D, Scheidereit C, Stein H et al (1999) Overexpression of I Kappa B alpha without inhibition of NF-Kappa B activity and mutations in the I Kappa B alpha gene in Reed–Sternberg cells. Blood 94:3129–3134PubMed Emmerich F, Meiser M, Hummel M, Demel G, Foss HD, Jundt F, Mathas S, Krappmann D, Scheidereit C, Stein H et al (1999) Overexpression of I Kappa B alpha without inhibition of NF-Kappa B activity and mutations in the I Kappa B alpha gene in Reed–Sternberg cells. Blood 94:3129–3134PubMed
33.
34.
Zurück zum Zitat Klement JF, Rice NR, Car BD, Abbondanzo SJ, Powers GD, Bhatt PH, Chen CH, Rosen CA, Stewart CL (1996) I Kappa B alpha deficiency results in a sustained NF-Kappa B response and severe widespread dermatitis in mice. Mol Cell Biol 16:2341–2349PubMed Klement JF, Rice NR, Car BD, Abbondanzo SJ, Powers GD, Bhatt PH, Chen CH, Rosen CA, Stewart CL (1996) I Kappa B alpha deficiency results in a sustained NF-Kappa B response and severe widespread dermatitis in mice. Mol Cell Biol 16:2341–2349PubMed
Metadaten
Titel
IkBα promoter polymorphisms in patients with ankylosing spondylitis
verfasst von
Yu-Hung Hung
Tsan-Teng Ou
Chia-Hui Lin
Ruei-Nian Li
Yu-Chih Lin
Wen-Chan Tsai
Hong-Wen Liu
Jeng-Hsien Yen
Publikationsdatum
01.11.2009
Verlag
Springer-Verlag
Erschienen in
Rheumatology International / Ausgabe 1/2009
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-009-0923-6

Weitere Artikel der Ausgabe 1/2009

Rheumatology International 1/2009 Zur Ausgabe

Acknowledgement to Referees

Referees 2008

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.