RGD Reference Report - Variation in the lymphotoxin-alpha/tumor necrosis factor locus modifies risk of erythema nodosum in sarcoidosis. - Rat Genome Database

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Variation in the lymphotoxin-alpha/tumor necrosis factor locus modifies risk of erythema nodosum in sarcoidosis.

Authors: McDougal, KE  Fallin, MD  Moller, DR  Song, Z  Cutler, DJ  Steiner, LL  Cutting, GR   
Citation: McDougal KE, etal., J Invest Dermatol. 2009 Aug;129(8):1921-6. doi: 10.1038/jid.2008.456. Epub 2009 Feb 19.
RGD ID: 8548773
Pubmed: PMID:19225544   (View Abstract at PubMed)
PMCID: PMC2877485   (View Article at PubMed Central)
DOI: DOI:10.1038/jid.2008.456   (Journal Full-text)

Sarcoidosis is a multi-system inflammatory disease with organ involvement that varies by race and sex. Family studies indicate that genes play a role in the etiology and extent of organ involvement in sarcoidosis. In this study, we evaluated whether 25 variants distributed in 19 genes with a known role in inflammation were associated with erythema nodosum status in 659 sarcoidosis patients and 658 controls from A Case-Control Etiologic Study of Sarcoidosis (ACCESS). We found no association with affectation status; however, a variant in the promoter of tumor necrosis factor (TNF) at position -308 was found to be associated with erythema nodosum in Caucasian sarcoidosis patients (study-wide P=0.027). When separated by sex, a variant in intron 1 of lymphotoxin-alpha (LTA), a gene adjacent to TNF, was associated with erythema nodosum in female Caucasian sarcoidosis patients (study-wide P=0.027). These DNA variants frequently occur together in Caucasians, and each variant has individually been associated with erythema nodosum in sarcoidosis patients. These results confirm that variation in the LTA/TNF gene cluster modifies a major skin manifestation of sarcoidosis and may explain the higher rate of erythema nodosum in females with sarcoidosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LTAHumanerythema nodosum  IAGP associated with Sarcoidosis;DNA:polymorphism:intronRGD 
LtaRaterythema nodosum  ISORGD:1345394associated with Sarcoidosis;DNA:polymorphism:intronRGD 
LtaMouseerythema nodosum  ISORGD:1345394associated with Sarcoidosis;DNA:polymorphism:intronRGD 

Objects Annotated

Genes (Rattus norvegicus)
Lta  (lymphotoxin alpha)

Genes (Mus musculus)
Lta  (lymphotoxin A)

Genes (Homo sapiens)
LTA  (lymphotoxin alpha)


Additional Information