Variation in the lymphotoxin-alpha/tumor necrosis factor locus modifies risk of erythema nodosum in sarcoidosis.
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.
McDougal
Kathryn E
KE
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Fallin
M Daniele
MD
Moller
David R
DR
Song
Zhimin
Z
Cutler
David J
DJ
Steiner
Lori L
LL
Cutting
Garry R
GR
D001741:Black or African American; D004893:Erythema Nodosum / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012507:Sarcoidosis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha