mRNA Expression of Cytochrome P450 17αhydroxylase, Cytochrome P450 Aromatase, Anti-Müllerian Hormone, Estrogen Receptor α, and Androgen Receptor in Developing Gonads of Japanese Quail

Japanese quail (Coturnix coturnix japonica) is widely used in avian reproduction tests and avian sex reversal screening tests for evaluating adverse effects of endocrine disrupting chemicals (EDCs). However, there are few reports on the molecular biological profiles during the development and sexual differentiation of the gonads in Japanese quail. In the present study, we investigated mRNA expression of cytochrome P450 17αhydroxylase (P450c17), cytochrome P450 aromatase (P450arom), anti-Müllerian hormone (AMH), estrogen receptor α (ERα) and androgen receptor (AR) in the embryonic and post-hatching gonads of Japanese quail by using real-time RT-PCR. The left gonads of male and female Japanese quail at 16 days of incubation and 3, 7 and 14 days after hatching were used in the study. P450c17 mRNA expression in females was significantly higher than that in males at 16 days of incubation, 3 and 7 days after hatching. P450arom mRNA expression in females was markedly higher than that in males and there were significant differences at 3, 7 and 14 days after hatching. AMH mRNA expression in males was apparently higher than that in females and there were significant differences at 16 days of incubation and 3 days after hatching. ERα mRNA was highly expressed not only in females but also in males at 16 days of incubation. There were no meaningful trends of AR mRNA expressions in male and female gonads during the observation periods. It is likely that the profiles of mRNA expression of P450c17, P450arom, AMH, ERα and AR in the embryonic and post-hatching gonads of normal Japanese quail in the present study provide basic and useful information

POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33

Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4, 045 Japanese individuals (2, 060 cases and 1, 985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10⁻⁹). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10⁻⁸). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC

Summary of the current status of clinically diagnosed cases of Schnitzler syndrome in Japan

Background: Schnitzler syndrome is a rare disorder with chronic urticaria, and there is no report summarizing the current status in Japan. Methods: A nationwide survey of major dermatology departments in Japan was conducted in 2019. We further performed a systematic search of PubMed and Ichushi-Web, using the keywords “Schnitzler syndrome” and “Japan” then contacted the corresponding authors or physicians for further information. Results: Excluding duplicates, a total of 36 clinically diagnosed cases were identified from 1994 through the spring of 2022, with a male to female ratio of 1:1. The median age of onset was 56.5 years. It took 3.3 years from the first symptom, mostly urticaria, to reach the final diagnosis. The current status of 30 cases was ascertained; two patients developed B-cell lymphoma. SchS treatment was generally effective with high doses of corticosteroids, but symptoms sometimes recurred after tapering. Colchicine was administered in 17 cases and was effective in 8, but showed no effect in the others. Tocilizumab, used in six cases, improved laboratory abnormalities and symptoms, but lost its efficacy after several years. Rituximab, used in five cases, was effective in reducing serum IgM levels or lymphoma mass, but not in inflammatory symptoms. Four cases were treated with IL-1 targeting therapy, either anakinra or canakinumab, and achieved complete remission, except one case with diffuse large B-cell lymphoma. Conclusions: Since Schnitzler syndrome is a rare disease, the continuous collection and long-term follow-up of clinical information is essential for its appropriate treatment and further understanding of its pathophysiology