Variation in the lymphotoxin-alpha/tumor necrosis factor locus modifies risk of erythema nodosum in sarcoidosis.
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| 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 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.
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| Authors | Kathryn E McDougal, M Daniele Fallin, David R Moller, Zhimin Song, David J Cutler, Lori L Steiner, Garry R Cutting, ACCESS Research Group |
| Journal | The Journal of investigative dermatology (J Invest Dermatol) Vol. 129 Issue 8 Pg. 1921-6 (Aug 2009) ISSN: 1523-1747 [Electronic] United States |
| PMID | 19225544 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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