Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci

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

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Abstract

Purpose. The white-dot syndromes are a heterogenous group of chorioretinal disorders that have many common clinical features. Whether these disorders represent distinct clinical entities or different manifestations of the same disease warrants further interrogation. Two white-dot syndromes were investigated, with closely overlapping phenotypes-multifocal choroiditis with panuveitis (MFCPU) and punctate inner choroidopathy (PIC)-for differences in clinical course and genotype frequency at IL10 and TNF loci, known to be associated with noninfectious uveitis. Methods. Twelve polymorphisms were genotyped, spanning the TNFA and IL10 genomic regions, in 61 patients with MFCPU or PIC and 92 population controls from the United Kingdom and Republic of Ireland. Results. There were clear differences in clinical course between patients with MFCPU and PIC which had prognostic significance. However, both patient groups demonstrated similar associations with the IL10 haplotype, IL10htSNP2(-2849)AX/htSNP5(+434)TC and negative associations with the TNF haplotype, LTA+252A/TNFhtSNP1(-308)G/TNFhtSNP2(-238)G/TNFhtSNP3(+488)A/TNFd3. Conclusions. Despite clear differences in clinical course and outcome, MFCPU and PIC may still represent two manifestations of the same disease, given their similar genetic associations with IL10 and TNF loci, which are known to be associated with noninfectious uveitis and autoimmunity, in general. Definitive proof will necessitate genomewide sequence analysis. However, the data also support the notion that epigenetic factors have a strong effect on clinical phenotype.
Original languageEnglish
Pages (from-to)3573-3581
Number of pages9
JournalInvestigative Ophthalmology & Visual Science
Volume52
Issue number6
DOIs
Publication statusPublished - 26 May 2011

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Panuveitis
Interleukin-10
Uveitis
Haplotypes
Phenotype
Population Control
Autoimmunity
Ireland
Epigenomics
Sequence Analysis
Genotype
Multifocal choroiditis

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Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci. / Atan, Denize; Fraser-Bell, Samantha; Plskova, Jarka; Kuffova, Lucia; Hogan, Aideen; Tufail, Adnan; Kilmartin, Dara J; Forrester, John V; Bidwell, Jeff L; Dick, Andrew D; Churchill, Amanda J.

In: Investigative Ophthalmology & Visual Science, Vol. 52, No. 6, 26.05.2011, p. 3573-3581.

Research output: Contribution to journalArticle

Atan, D, Fraser-Bell, S, Plskova, J, Kuffova, L, Hogan, A, Tufail, A, Kilmartin, DJ, Forrester, JV, Bidwell, JL, Dick, AD & Churchill, AJ 2011, 'Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci', Investigative Ophthalmology & Visual Science, vol. 52, no. 6, pp. 3573-3581. https://doi.org/10.1167/iovs.10-6743
Atan, Denize ; Fraser-Bell, Samantha ; Plskova, Jarka ; Kuffova, Lucia ; Hogan, Aideen ; Tufail, Adnan ; Kilmartin, Dara J ; Forrester, John V ; Bidwell, Jeff L ; Dick, Andrew D ; Churchill, Amanda J. / Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci. In: Investigative Ophthalmology & Visual Science. 2011 ; Vol. 52, No. 6. pp. 3573-3581.
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abstract = "Purpose. The white-dot syndromes are a heterogenous group of chorioretinal disorders that have many common clinical features. Whether these disorders represent distinct clinical entities or different manifestations of the same disease warrants further interrogation. Two white-dot syndromes were investigated, with closely overlapping phenotypes-multifocal choroiditis with panuveitis (MFCPU) and punctate inner choroidopathy (PIC)-for differences in clinical course and genotype frequency at IL10 and TNF loci, known to be associated with noninfectious uveitis. Methods. Twelve polymorphisms were genotyped, spanning the TNFA and IL10 genomic regions, in 61 patients with MFCPU or PIC and 92 population controls from the United Kingdom and Republic of Ireland. Results. There were clear differences in clinical course between patients with MFCPU and PIC which had prognostic significance. However, both patient groups demonstrated similar associations with the IL10 haplotype, IL10htSNP2(-2849)AX/htSNP5(+434)TC and negative associations with the TNF haplotype, LTA+252A/TNFhtSNP1(-308)G/TNFhtSNP2(-238)G/TNFhtSNP3(+488)A/TNFd3. Conclusions. Despite clear differences in clinical course and outcome, MFCPU and PIC may still represent two manifestations of the same disease, given their similar genetic associations with IL10 and TNF loci, which are known to be associated with noninfectious uveitis and autoimmunity, in general. Definitive proof will necessitate genomewide sequence analysis. However, the data also support the notion that epigenetic factors have a strong effect on clinical phenotype.",
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T1 - Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci

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 L

AU - Dick, Andrew D

AU - Churchill, Amanda J

PY - 2011/5/26

Y1 - 2011/5/26

N2 - Purpose. The white-dot syndromes are a heterogenous group of chorioretinal disorders that have many common clinical features. Whether these disorders represent distinct clinical entities or different manifestations of the same disease warrants further interrogation. Two white-dot syndromes were investigated, with closely overlapping phenotypes-multifocal choroiditis with panuveitis (MFCPU) and punctate inner choroidopathy (PIC)-for differences in clinical course and genotype frequency at IL10 and TNF loci, known to be associated with noninfectious uveitis. Methods. Twelve polymorphisms were genotyped, spanning the TNFA and IL10 genomic regions, in 61 patients with MFCPU or PIC and 92 population controls from the United Kingdom and Republic of Ireland. Results. There were clear differences in clinical course between patients with MFCPU and PIC which had prognostic significance. However, both patient groups demonstrated similar associations with the IL10 haplotype, IL10htSNP2(-2849)AX/htSNP5(+434)TC and negative associations with the TNF haplotype, LTA+252A/TNFhtSNP1(-308)G/TNFhtSNP2(-238)G/TNFhtSNP3(+488)A/TNFd3. Conclusions. Despite clear differences in clinical course and outcome, MFCPU and PIC may still represent two manifestations of the same disease, given their similar genetic associations with IL10 and TNF loci, which are known to be associated with noninfectious uveitis and autoimmunity, in general. Definitive proof will necessitate genomewide sequence analysis. However, the data also support the notion that epigenetic factors have a strong effect on clinical phenotype.

AB - Purpose. The white-dot syndromes are a heterogenous group of chorioretinal disorders that have many common clinical features. Whether these disorders represent distinct clinical entities or different manifestations of the same disease warrants further interrogation. Two white-dot syndromes were investigated, with closely overlapping phenotypes-multifocal choroiditis with panuveitis (MFCPU) and punctate inner choroidopathy (PIC)-for differences in clinical course and genotype frequency at IL10 and TNF loci, known to be associated with noninfectious uveitis. Methods. Twelve polymorphisms were genotyped, spanning the TNFA and IL10 genomic regions, in 61 patients with MFCPU or PIC and 92 population controls from the United Kingdom and Republic of Ireland. Results. There were clear differences in clinical course between patients with MFCPU and PIC which had prognostic significance. However, both patient groups demonstrated similar associations with the IL10 haplotype, IL10htSNP2(-2849)AX/htSNP5(+434)TC and negative associations with the TNF haplotype, LTA+252A/TNFhtSNP1(-308)G/TNFhtSNP2(-238)G/TNFhtSNP3(+488)A/TNFd3. Conclusions. Despite clear differences in clinical course and outcome, MFCPU and PIC may still represent two manifestations of the same disease, given their similar genetic associations with IL10 and TNF loci, which are known to be associated with noninfectious uveitis and autoimmunity, in general. Definitive proof will necessitate genomewide sequence analysis. However, the data also support the notion that epigenetic factors have a strong effect on clinical phenotype.

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DO - 10.1167/iovs.10-6743

M3 - Article

VL - 52

SP - 3573

EP - 3581

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

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ER -