TNFRSF1B Is Associated with ANCA in IBD.
The genetic basis of antineutrophil cytoplasmic antibody, an important biomarker of inflammatory bowel disease (IBD), has never been thoroughly examined on a genome-wide scale. In this study, we performed a 2-stage genome-wide association study (GWAS) on antineutrophil cytoplasmic antibody in IBD cases. In the 2959 IBD cases in the discovery stage, we observed an association between a variant in the gene TNFRSF1B with antineutrophil cytoplasmic antibody level (rs5745994, minor allele frequency = 0.028, beta = 18.12, 95% CI, 11.82-24.22, P = 1.89 × 10). This association was replicated in an independent cohort of 419 IBD cases (beta = 16.91, 95% CI, 6.13-27.69, P = 2.38 × 10). With a Q-value of 0.036, we performed a fixed-effect meta-analysis for the association of rs5745994 in both cohorts and observed a stronger association signal (beta = 17.81, 95% CI, 12.36-23.25, P = 8.97 × 10). TNFRSF1B gene codes for tumor necrosis factor (TNF) receptor 2 (TNFR2), thereby we examined the reported TNFRSF1B variant with serum TNFR2 level. We observed a negative association with serum TNFR2 level being 8.23 EU/mL in carriers and 9.12 EU/mL in noncarriers (P = 0.033). This finding indicates the functional role of identified TNFRSF1B variant in IBD serology and may be reflective of the underlying biological mechanisms that determine clinical expression and/or response to certain therapies.
*Department of Medicine, F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; †Mount Sinai Hospital, Toronto, Ontario, Canada; ‡The Susan and Leonard Feinstein IBD Clinical Center, East New York, New York; and §Institute for Translational Genomics and Population Science, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California.
Dalin
D
Li
Mark S
MS
Silverberg
Talin
T
Haritunians
Marla C
MC
Dubinsky
Carol
C
Landers
Joanne M
JM
Stempak
Raquel
R
Milgrom
Xiuqing
X
Guo
Yii-Der Ida
YD
Chen
Jerome I
JI
Rotter
Kent D
KD
Taylor
Dermot P B
DP
McGovern
Stephan R
SR
Targan
D000293:Adolescent; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology; D005260:Female; D055106:Genome-Wide Association Study; D006579:Heterozygote; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology*; D008297:Male; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
D019268:Antibodies, Antineutrophil Cytoplasmic; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human