title: Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci.
abstract: OBJECTIVE
  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.
authors.affiliation: School of Clinical Sciences, Bristol Eye Hospital, Bristol, United Kingdom. denize.atan@bristol.ac.uk
authors.forename: Denize
authors.initials: D
authors.lastname: Atan
authors.forename: Samantha
authors.initials: S
authors.lastname: Fraser-Bell
authors.forename: Jarka
authors.initials: J
authors.lastname: Plskova
authors.forename: Lucia
authors.initials: L
authors.lastname: Kuffová
authors.forename: Aideen
authors.initials: A
authors.lastname: Hogan
authors.forename: Adnan
authors.initials: A
authors.lastname: Tufail
authors.forename: Dara J
authors.initials: DJ
authors.lastname: Kilmartin
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Bidwell
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Dick
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Churchill
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002833:Choroiditis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015864:Panuveitis / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10