Cytokine polymorphism in noninfectious uveitis

Denize Atan, Samantha Fraser-Bell, Jarka Plskova, Lucia Kuffova, Aideen Hogan, Adnan Tufail, Dara J. Kilmartin, John V. Forrester, Jeff Bidwell, Andrew D. Dick, Amanda J. Churchill

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Purpose. Noninfectious uveitis is a sight-threatening immune-mediated intraocular inflammatory disorder. The inheritance of uveitis in multiplex families and its association with known monogenic and polygenic immunologic disorders suggests that common genetic variants underlie susceptibility to uveitis as well as to other immunologic disorders. TNFA and IL10 are strong candidate genes, given the influence of these cytokines on inflammation, immune tolerance, and apoptosis.

Methods. The role of 12 polymorphisms spanning the TNFA and IL10 genomic regions was investigated in 192 uveitis patients and 92 population control subjects from four regional centers in the United Kingdom and Republic of Ireland.

Results. The results demonstrate that uveitis is associated with three haplotype-tagging SNPs (htSNPs) in the IL10 gene: htSNP2 (rs6703630), htSNP5 (rs2222202), and htSNP6 (rs3024490). IL10htSNP2AG/htSNP5TC was the most significantly associated haplotype (P = 0.00085), whereas the LTA+252AA/TNFhtSNP2GG haplotype was protective (P = 0.00031). Furthermore, subgroup analysis showed that the frequency of the TNFd4 allele was higher in patients with nonremitting ocular disease and/or those requiring higher levels of maintenance immunosuppression. Although these associations lost significance after Bonferroni correction, they infer a relationship that may be validated by a larger study.

Conclusions. Since these variants are implicated in the susceptibility and severity of several immunologic disorders, the results support the hypothesis that common genetic determinants influence shared mechanisms of autoimmunity.
Original languageEnglish
Pages (from-to)4133-4142
Number of pages10
JournalInvestigative Ophthalmology & Visual Science
Volume51
Issue number8
Early online date24 Mar 2010
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Uveitis
Cytokines
Interleukin-10
Haplotypes
Immune Tolerance
Population Control
Eye Diseases
Autoimmunity
Ireland
Gene Frequency
Immunosuppression
Genes
Single Nucleotide Polymorphism
Maintenance
Apoptosis
Inflammation

Cite this

Atan, D., Fraser-Bell, S., Plskova, J., Kuffova, L., Hogan, A., Tufail, A., ... Churchill, A. J. (2010). Cytokine polymorphism in noninfectious uveitis. Investigative Ophthalmology & Visual Science, 51(8), 4133-4142. https://doi.org/10.1167/iovs.09-4583

Cytokine polymorphism in noninfectious uveitis. / Atan, Denize; Fraser-Bell, Samantha; Plskova, Jarka; Kuffova, Lucia; Hogan, Aideen; Tufail, Adnan; Kilmartin, Dara J.; Forrester, John V.; Bidwell, Jeff; Dick, Andrew D.; Churchill, Amanda J.

In: Investigative Ophthalmology & Visual Science, Vol. 51, No. 8, 08.2010, p. 4133-4142.

Research output: Contribution to journalArticle

Atan, D, Fraser-Bell, S, Plskova, J, Kuffova, L, Hogan, A, Tufail, A, Kilmartin, DJ, Forrester, JV, Bidwell, J, Dick, AD & Churchill, AJ 2010, 'Cytokine polymorphism in noninfectious uveitis', Investigative Ophthalmology & Visual Science, vol. 51, no. 8, pp. 4133-4142. https://doi.org/10.1167/iovs.09-4583
Atan D, Fraser-Bell S, Plskova J, Kuffova L, Hogan A, Tufail A et al. Cytokine polymorphism in noninfectious uveitis. Investigative Ophthalmology & Visual Science. 2010 Aug;51(8):4133-4142. https://doi.org/10.1167/iovs.09-4583
Atan, Denize ; Fraser-Bell, Samantha ; Plskova, Jarka ; Kuffova, Lucia ; Hogan, Aideen ; Tufail, Adnan ; Kilmartin, Dara J. ; Forrester, John V. ; Bidwell, Jeff ; Dick, Andrew D. ; Churchill, Amanda J. / Cytokine polymorphism in noninfectious uveitis. In: Investigative Ophthalmology & Visual Science. 2010 ; Vol. 51, No. 8. pp. 4133-4142.
@article{35612c43fcb140aeab4369ae23dfc003,
title = "Cytokine polymorphism in noninfectious uveitis",
abstract = "Purpose. Noninfectious uveitis is a sight-threatening immune-mediated intraocular inflammatory disorder. The inheritance of uveitis in multiplex families and its association with known monogenic and polygenic immunologic disorders suggests that common genetic variants underlie susceptibility to uveitis as well as to other immunologic disorders. TNFA and IL10 are strong candidate genes, given the influence of these cytokines on inflammation, immune tolerance, and apoptosis.Methods. The role of 12 polymorphisms spanning the TNFA and IL10 genomic regions was investigated in 192 uveitis patients and 92 population control subjects from four regional centers in the United Kingdom and Republic of Ireland.Results. The results demonstrate that uveitis is associated with three haplotype-tagging SNPs (htSNPs) in the IL10 gene: htSNP2 (rs6703630), htSNP5 (rs2222202), and htSNP6 (rs3024490). IL10htSNP2AG/htSNP5TC was the most significantly associated haplotype (P = 0.00085), whereas the LTA+252AA/TNFhtSNP2GG haplotype was protective (P = 0.00031). Furthermore, subgroup analysis showed that the frequency of the TNFd4 allele was higher in patients with nonremitting ocular disease and/or those requiring higher levels of maintenance immunosuppression. Although these associations lost significance after Bonferroni correction, they infer a relationship that may be validated by a larger study.Conclusions. Since these variants are implicated in the susceptibility and severity of several immunologic disorders, the results support the hypothesis that common genetic determinants influence shared mechanisms of autoimmunity.",
author = "Denize Atan and Samantha Fraser-Bell and Jarka Plskova and Lucia Kuffova and Aideen Hogan and Adnan Tufail and Kilmartin, {Dara J.} and Forrester, {John V.} and Jeff Bidwell and Dick, {Andrew D.} and Churchill, {Amanda J.}",
year = "2010",
month = "8",
doi = "10.1167/iovs.09-4583",
language = "English",
volume = "51",
pages = "4133--4142",
journal = "Investigative Ophthalmology & Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "8",

}

TY - JOUR

T1 - Cytokine polymorphism in noninfectious uveitis

AU - Atan, Denize

AU - Fraser-Bell, Samantha

AU - Plskova, Jarka

AU - Kuffova, Lucia

AU - Hogan, Aideen

AU - Tufail, Adnan

AU - Kilmartin, Dara J.

AU - Forrester, John V.

AU - Bidwell, Jeff

AU - Dick, Andrew D.

AU - Churchill, Amanda J.

PY - 2010/8

Y1 - 2010/8

N2 - Purpose. Noninfectious uveitis is a sight-threatening immune-mediated intraocular inflammatory disorder. The inheritance of uveitis in multiplex families and its association with known monogenic and polygenic immunologic disorders suggests that common genetic variants underlie susceptibility to uveitis as well as to other immunologic disorders. TNFA and IL10 are strong candidate genes, given the influence of these cytokines on inflammation, immune tolerance, and apoptosis.Methods. The role of 12 polymorphisms spanning the TNFA and IL10 genomic regions was investigated in 192 uveitis patients and 92 population control subjects from four regional centers in the United Kingdom and Republic of Ireland.Results. The results demonstrate that uveitis is associated with three haplotype-tagging SNPs (htSNPs) in the IL10 gene: htSNP2 (rs6703630), htSNP5 (rs2222202), and htSNP6 (rs3024490). IL10htSNP2AG/htSNP5TC was the most significantly associated haplotype (P = 0.00085), whereas the LTA+252AA/TNFhtSNP2GG haplotype was protective (P = 0.00031). Furthermore, subgroup analysis showed that the frequency of the TNFd4 allele was higher in patients with nonremitting ocular disease and/or those requiring higher levels of maintenance immunosuppression. Although these associations lost significance after Bonferroni correction, they infer a relationship that may be validated by a larger study.Conclusions. Since these variants are implicated in the susceptibility and severity of several immunologic disorders, the results support the hypothesis that common genetic determinants influence shared mechanisms of autoimmunity.

AB - Purpose. Noninfectious uveitis is a sight-threatening immune-mediated intraocular inflammatory disorder. The inheritance of uveitis in multiplex families and its association with known monogenic and polygenic immunologic disorders suggests that common genetic variants underlie susceptibility to uveitis as well as to other immunologic disorders. TNFA and IL10 are strong candidate genes, given the influence of these cytokines on inflammation, immune tolerance, and apoptosis.Methods. The role of 12 polymorphisms spanning the TNFA and IL10 genomic regions was investigated in 192 uveitis patients and 92 population control subjects from four regional centers in the United Kingdom and Republic of Ireland.Results. The results demonstrate that uveitis is associated with three haplotype-tagging SNPs (htSNPs) in the IL10 gene: htSNP2 (rs6703630), htSNP5 (rs2222202), and htSNP6 (rs3024490). IL10htSNP2AG/htSNP5TC was the most significantly associated haplotype (P = 0.00085), whereas the LTA+252AA/TNFhtSNP2GG haplotype was protective (P = 0.00031). Furthermore, subgroup analysis showed that the frequency of the TNFd4 allele was higher in patients with nonremitting ocular disease and/or those requiring higher levels of maintenance immunosuppression. Although these associations lost significance after Bonferroni correction, they infer a relationship that may be validated by a larger study.Conclusions. Since these variants are implicated in the susceptibility and severity of several immunologic disorders, the results support the hypothesis that common genetic determinants influence shared mechanisms of autoimmunity.

U2 - 10.1167/iovs.09-4583

DO - 10.1167/iovs.09-4583

M3 - Article

VL - 51

SP - 4133

EP - 4142

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 8

ER -