Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis

Denize Atan, Jarka Heissigerova, Lucia Kuffova, Aideen Hogan, Dara J Kilmartin, John Vincent Forrester, Jeff L Bidwell, Andrew D. Dick, Amanda J Churchill

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Purpose: Idiopathic intermediate uveitis (IIU) is a potentially sight-threatening inflammatory disorder with welldefined anatomic diagnostic criteria. It is often associated with multiple sclerosis, and both conditions are linked to
HLA-DRB1*15. Previously, we have shown that non-infectious uveitis (NIU) is associated with interleukin 10 (IL10)
polymorphisms, IL10-2849A (rs6703630), IL10+434T (rs2222202), and IL10+504G (rs3024490), while a LTA+252AA/
TNFA-238GG haplotype (rs909253/rs361525) is protective. In this study, we determined whether patients with IIU have
a similar genetic profile as patients with NIU or multiple sclerosis.
Methods: Twelve polymorphisms were genotyped, spanning the tumor necrosis factor (TNF) and IL10 genomic regions,
in 44 patients with IIU and 92 population controls from the UK and the Republic of Ireland.
Results: IIU was strongly associated with the TNFA-308A and TNFA-238A polymorphisms. We found the combination
of TNFA-308 and -238 loci was more strongly associated with IIU than any other loci across the major histocompatibility
complex, including HLA-DRB1.
Conclusions: TNF polymorphisms, associated with increased TNF production, are highly associated with IIU. These
results offer the potential to ascribe therapeutic response and risk (i.e., the influence of HLA-DRB1*15 status and TNFR1
polymorphism) to anti-TNF therapy in IIU.
Original languageEnglish
Pages (from-to)184-195
Number of pages12
JournalMolecular vision
Volume19
Publication statusPublished - 28 Jan 2013

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Intermediate Uveitis
Tumor Necrosis Factor-alpha
Interleukin-10
HLA-DRB1 Chains
Uveitis
Multiple Sclerosis
Population Control
Major Histocompatibility Complex
Ireland
Haplotypes

Cite this

Atan, D., Heissigerova, J., Kuffova, L., Hogan, A., Kilmartin, D. J., Forrester, J. V., ... Churchill, A. J. (2013). Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis. Molecular vision, 19, 184-195.

Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis. / Atan, Denize; Heissigerova, Jarka; Kuffova, Lucia; Hogan, Aideen; Kilmartin, Dara J; Forrester, John Vincent; Bidwell, Jeff L; Dick, Andrew D.; Churchill, Amanda J.

In: Molecular vision, Vol. 19, 28.01.2013, p. 184-195.

Research output: Contribution to journalArticle

Atan, D, Heissigerova, J, Kuffova, L, Hogan, A, Kilmartin, DJ, Forrester, JV, Bidwell, JL, Dick, AD & Churchill, AJ 2013, 'Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis', Molecular vision, vol. 19, pp. 184-195.
Atan D, Heissigerova J, Kuffova L, Hogan A, Kilmartin DJ, Forrester JV et al. Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis. Molecular vision. 2013 Jan 28;19:184-195.
Atan, Denize ; Heissigerova, Jarka ; Kuffova, Lucia ; Hogan, Aideen ; Kilmartin, Dara J ; Forrester, John Vincent ; Bidwell, Jeff L ; Dick, Andrew D. ; Churchill, Amanda J. / Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis. In: Molecular vision. 2013 ; Vol. 19. pp. 184-195.
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abstract = "Purpose: Idiopathic intermediate uveitis (IIU) is a potentially sight-threatening inflammatory disorder with welldefined anatomic diagnostic criteria. It is often associated with multiple sclerosis, and both conditions are linked to HLA-DRB1*15. Previously, we have shown that non-infectious uveitis (NIU) is associated with interleukin 10 (IL10) polymorphisms, IL10-2849A (rs6703630), IL10+434T (rs2222202), and IL10+504G (rs3024490), while a LTA+252AA/TNFA-238GG haplotype (rs909253/rs361525) is protective. In this study, we determined whether patients with IIU have a similar genetic profile as patients with NIU or multiple sclerosis.Methods: Twelve polymorphisms were genotyped, spanning the tumor necrosis factor (TNF) and IL10 genomic regions, in 44 patients with IIU and 92 population controls from the UK and the Republic of Ireland.Results: IIU was strongly associated with the TNFA-308A and TNFA-238A polymorphisms. We found the combination of TNFA-308 and -238 loci was more strongly associated with IIU than any other loci across the major histocompatibility complex, including HLA-DRB1.Conclusions: TNF polymorphisms, associated with increased TNF production, are highly associated with IIU. These results offer the potential to ascribe therapeutic response and risk (i.e., the influence of HLA-DRB1*15 status and TNFR1polymorphism) to anti-TNF therapy in IIU.",
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AU - Kuffova, Lucia

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AU - Kilmartin, Dara J

AU - Forrester, John Vincent

AU - Bidwell, Jeff L

AU - Dick, Andrew D.

AU - Churchill, Amanda J

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N2 - Purpose: Idiopathic intermediate uveitis (IIU) is a potentially sight-threatening inflammatory disorder with welldefined anatomic diagnostic criteria. It is often associated with multiple sclerosis, and both conditions are linked to HLA-DRB1*15. Previously, we have shown that non-infectious uveitis (NIU) is associated with interleukin 10 (IL10) polymorphisms, IL10-2849A (rs6703630), IL10+434T (rs2222202), and IL10+504G (rs3024490), while a LTA+252AA/TNFA-238GG haplotype (rs909253/rs361525) is protective. In this study, we determined whether patients with IIU have a similar genetic profile as patients with NIU or multiple sclerosis.Methods: Twelve polymorphisms were genotyped, spanning the tumor necrosis factor (TNF) and IL10 genomic regions, in 44 patients with IIU and 92 population controls from the UK and the Republic of Ireland.Results: IIU was strongly associated with the TNFA-308A and TNFA-238A polymorphisms. We found the combination of TNFA-308 and -238 loci was more strongly associated with IIU than any other loci across the major histocompatibility complex, including HLA-DRB1.Conclusions: TNF polymorphisms, associated with increased TNF production, are highly associated with IIU. These results offer the potential to ascribe therapeutic response and risk (i.e., the influence of HLA-DRB1*15 status and TNFR1polymorphism) to anti-TNF therapy in IIU.

AB - Purpose: Idiopathic intermediate uveitis (IIU) is a potentially sight-threatening inflammatory disorder with welldefined anatomic diagnostic criteria. It is often associated with multiple sclerosis, and both conditions are linked to HLA-DRB1*15. Previously, we have shown that non-infectious uveitis (NIU) is associated with interleukin 10 (IL10) polymorphisms, IL10-2849A (rs6703630), IL10+434T (rs2222202), and IL10+504G (rs3024490), while a LTA+252AA/TNFA-238GG haplotype (rs909253/rs361525) is protective. In this study, we determined whether patients with IIU have a similar genetic profile as patients with NIU or multiple sclerosis.Methods: Twelve polymorphisms were genotyped, spanning the tumor necrosis factor (TNF) and IL10 genomic regions, in 44 patients with IIU and 92 population controls from the UK and the Republic of Ireland.Results: IIU was strongly associated with the TNFA-308A and TNFA-238A polymorphisms. We found the combination of TNFA-308 and -238 loci was more strongly associated with IIU than any other loci across the major histocompatibility complex, including HLA-DRB1.Conclusions: TNF polymorphisms, associated with increased TNF production, are highly associated with IIU. These results offer the potential to ascribe therapeutic response and risk (i.e., the influence of HLA-DRB1*15 status and TNFR1polymorphism) to anti-TNF therapy in IIU.

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