TNFRSF1B Is Associated with ANCA in IBD.

Abstract:

: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.

journal_name

Inflamm Bowel Dis

authors

Li D,Silverberg MS,Haritunians T,Dubinsky MC,Landers C,Stempak JM,Milgrom R,Guo X,Chen YD,Rotter JI,Taylor KD,McGovern DP,Targan SR

doi

10.1097/MIB.0000000000000771

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

1346-52

issue

6

eissn

1078-0998

issn

1536-4844

journal_volume

22

pub_type

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