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

Kathryn E. McDougal, M. Daniele Fallin, David R. Moller, Zhimin Song, David J. Cutler, Lori L. Steiner, Garry R. Cutting

Research output: Contribution to journalArticlepeer-review

Abstract

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 P0.027). When separated by sex, a variant in intron 1 of lymphotoxin-α (LTA), a gene adjacent to TNF, was associated with erythema nodosum in female Caucasian sarcoidosis patients (study-wide P0.027). 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.

Original languageEnglish (US)
Pages (from-to)1921-1926
Number of pages6
JournalJournal of Investigative Dermatology
Volume129
Issue number8
DOIs
StatePublished - Aug 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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