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STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility

Genes & Immunity volume 11, pages 264–268 (2010)Cite this article

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Abstract

STAT3 (signal transducer and activator of transcription 3) signaling is a critical component of Th17-dependent autoimmune processes. Genome-wide association studies (GWAS) have revealed the role of the STAT3 gene in inflammatory bowel disease (IBD) susceptibility, although confirmation in clinical subphenotypes is warranted. Mice with targeted deletion of Stat3 in T cells are resistant to experimental autoimmune encephalomyelitis, which is a multiple sclerosis (MS) model. Moreover, increased phosphorylated STAT3 was reported in T cells of patients evolving from clinically isolated syndrome to defined MS and in relapsing patients. These evidences led us to analyze the role of STAT3 in Crohn's disease (CD), ulcerative colitis (UC) and MS risk. Polymorphisms in the STAT3 region (rs3809758/rs744166/rs1026916/rs12948909) were genotyped and the inferred haplotypes were subsequently analyzed in 860 IBD and 1540 MS Spanish patients and 1720 ethnically matched controls. The haplotype conformed by the risk alleles of each polymorphism was significantly associated with both clinical phenotypes of IBD (CD: P=0.005, odds ratio 1.25, 95% confidence interval 1.06–1.46; and UC: P=0.002, odds ratio 1.19, 95% confidence interval 1.02–1.38). No evidence of association was detected for MS. The originally described association of IBD with STAT3 polymorphisms is corroborated for the two clinical phenotypes, CD and UC, in an independent population. A major role of this gene in MS seems unlikely.

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Acknowledgements

We thank Carmen Martínez and Angel García for their skillful technical assistance. Elena Urcelay works for the Fundación para la Investigación Biomédica-Hospital Clínico San Carlos. This work was supported by grants from Fundación Alfonso Martín Escudero, Fundación Ramón Areces, Fondo de Investigaciones Sanitarias PI07/0353, PI08/1676, PI08/1636 and RETICS 2007 (REEM), PN-SAF2006-02023, Junta de Andalucía Tin2007-67418-C3-03, SAS PI0168/2007.

Author information

Author notes

  1. M C Cénit, A Alcina, A Márquez, F Matesanz and E Urcelay: These authors contributed equally to this work.

  2. V de las Heras, G Izquierdo, R Arroyo, O Fernández, E G de la Concha, F Matesanz and E Urcelay: Members of the Red Española de Esclerosis Múltiple (REEM), www.reem.es

Authors and Affiliations

  1. Immunology Department, Hospital Cl,

    M C Cénit, A Márquez, E G de la Concha & E Urcelay

  2. í,

    M C Cénit, A Márquez, E G de la Concha & E Urcelay

  3. nico S Carlos, Madrid, Spain

    M C Cénit, A Márquez, E G de la Concha & E Urcelay

  4. Instituto de Parasitolog,

    A Alcina & F Matesanz

  5. í,

    A Alcina & F Matesanz

  6. a y Biomedicina ‘L,

    A Alcina & F Matesanz

  7. ó,

    A Alcina & F Matesanz

  8. pez Neyra’, Consejo Superior de Investigaciones Cient,

    A Alcina & F Matesanz

  9. í,

    A Alcina & F Matesanz

  10. ficas, Granada, Spain

    A Alcina & F Matesanz

  11. Digestive Department, Hospital Cl,

    J L Mendoza & M Díaz-Rubio

  12. í,

    J L Mendoza & M Díaz-Rubio

  13. nico S Carlos, Madrid, Spain

    J L Mendoza & M Díaz-Rubio

  14. Neurology Department, Hospital Cl,

    V de las Heras & R Arroyo

  15. í,

    V de las Heras & R Arroyo

  16. nico S Carlos, Madrid, Spain

    V de las Heras & R Arroyo

  17. Unidad de Esclerosis M,

    G Izquierdo

  18. ú,

    G Izquierdo

  19. ltiple, Hospital Virgen Macarena, Sevilla, Spain

    G Izquierdo

  20. Servicio de Neurolog,

    O Fernández

  21. í,

    O Fernández

  22. a, Instituto de Neurociencias Cl,

    O Fernández

  23. í,

    O Fernández

  24. nicas, Hospital Carlos Haya, M, á, laga, Spain

    O Fernández

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  1. M C Cénit
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Correspondence to E Urcelay.

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Cénit, M., Alcina, A., Márquez, A. et al. STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility. Genes Immun 11, 264–268 (2010). https://doi.org/10.1038/gene.2010.10

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