Genome-wide association study identifies TNFSF15 and POU2AF1
as susceptibility loci for primary biliary cirrhosis in the Japanese population.
These genes include SERPINE2 , CD79A , and POU2AF1
.  In the current study, we observed that Alpha-1-AT is a susceptibility gene associated with COPD.
The 20 most up- and down-regulated genes include significant changes in expression of genes related to apoptosis (FDRX) B-cell functions (FCRLA, IGHM, PAX 5, BACH2, MS4A1, and POU2AF1
), inflammation (ITLN1, CCR7), hemoglobin synthesis (XK and RHD), and induced by oxidative stress (SESN3).
In this sense, genes like MEF2C, mTOR, MYB, FOXM1, GATA3, FOXP3, BCL6, MNDA, POU2AF1
, MEF2C, or SMAD3 have been reported to potentially regulate more than one thousand genes, which are transcriptional master regulators (TMRs) [2,3].
A subsequent noteworthy GWAS from Japan showed that the IL12A and IL12RB2 loci were not significantly associated with PBC, but rather that the TNFSF15 and POU2AF1
genes constituted novel risk loci in Japanese patients with PBC along with other non-HLA loci, including IL7R, IKZF3, CD80, STAT4, and NFKB1.
Among these, IL12A, IL12RB2, IRF5, TNPO3, DENND1B, SPIB, TNFAIP2, CXCR5, CLEC16A, RAD51L1, IRF8, RPS6KA4, MAP3K7IP1, TNFRSF1A, PLCL2, ELMO1, and ARF7 played an important role in the morbidity of PBC in European ancestries, while TNFSF15 and POU2AF1
were unique in Japanese ancestries, and CD80, IKZK3, Il7R, NFKB1, and STAT4 were proved to be associated with PBC in both races.
Kawashima et al., "Genome-wide association study identifies TNFSF15 and POU2AF1
as susceptibility loci for primary biliary cirrhosis in the Japanese population," American Journal of Human Genetics, vol.
Similarly, GWAS of the Japanese have identified novel significant susceptibility loci for PBC, such as TNFSF15 and POU2AF1
, which have not been identified in GWAS of populations of European descent.
Oct-1 and Oct-2 have been shown to interact with the coactivator BOB.1/OBF.1 (official symbol: Pou2af1
) and to promote OCT-dependent transcription [47-49].
There were ethnic differences in genetic susceptibility loci such as TNFSF15, POU2AF1
, IL12A, and IL12RB2 and common pathogenic pathways such as B cell differentiation, IL-12 signaling, and T cell activation.
In a new approach of transcriptional profiling at high temporal resolution, the chromatin regulator Mina, the TNF receptor Fas, Pou2af1
(OBF1), and Tsc22d3 were impressively proposed as new, specific factors of murine Th17 cells .
Heard et al., "Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1
as susceptibility genes in Europeans," Journal of Neuroimmunology, vol.