For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.

CTLA4 and SLC4A2 genetic polymorphisms are differentially associated with PBC development and progression, as well as anti-gp210 or anti-centromere antibody production, in Japanese PBC patients.

Organic-inorganic hybrid microcapsules (AP-capsules) were fabricated by sequential preparation of calcium alginate microcapsules (Alg-capsules), followed by the addition of the Alg-capsules to an aqueous solution of 3-aminopropyltriethoxysilane (APTES) in mild conditions without the use of any catalyst. Results showed that the shell thickness of AP-capsules was found to vary with time during the APTES incorporation onto the Alg-capsules, suggesting that the shell thickness was dependent on the amount of CaCl 2 contained initially in the core solution as well as on the reaction time. A model enzyme, formate dehydrogenase (FDH), was successfully encapsulated in AP-capsules, and maximum efficiency of encapsulation was found with the capsule size of 1 mm diameter. The AP-capsules were reused efficiently for 10 cycles without loss of FDH activity. The approach developed in this study could evolve as a generic platform of enzyme immobilization for biotechnology applications using core-shell microcapsule technology.

Sleep disorders at 16 weeks of gestation were the most significantly associated with threatened premature delivery.