The authors investigated 8 patients (4 Central Europeans, 3 Saudi Arabians and 1 Filipino) and found 3 distinct haplotypes; R1: a 7.2-kb deletion in the SLCO1B3

gene and c.1738CÇT (p.R580X) mutation in the SLCO1B1 gene, R2: a 405-kb deletion encompassing SLCO1B3 and SLCO1B1 genes, and R3: c. 1747+1G ÇA splice site mutation in the SLCO1B3 gene and c.757CÇT (p.R253X) mutation in the SLCO1B1 gene. In this study we aimed to elucidate whether these haplotypes were relevant to the occurrence of Rotor syndrome in Japan. Patients and Methods. We studied 3 patients who were diagnosed as having Rotor syndrome by laboratory data and laparoscopy. They consisted of a Filipina (P1) and 2 Japanese men (J1 and J2). We extracted genomic DNA from peripheral blood and analyzed the R1, R2 and R3 haplotypes by PCR and direct sequencing. We performed immunohistochemistry Dabrafenib mw for OATP1B1 and OATP1B3 proteins in liver tissues using specific antibodies. We also analyzed the allele frequency in 87 Japan-ese subjects. This study was approved by the Tokai University ethics committee. Results. Genetic analysis revealed that P1 had c.1747+1G ÇA splice site mutation

in the SLCO1B3 gene and c.757CÇT mutation in the SLCO1B1 gene homozygously, resulting in the R3 haplotype. Both J1 and J2 were homozygous Selleck ITF2357 for c.1738CÇT mutation in the SLCO1B1 gene, but the deletions or mutations in the SLCO1B3 gene recognized in the R1, R2 and R3 haplotypes were not detected.

We sequenced the entire coding regions of this gene, but could not find any mutations. Instead, a 6.5-kb homozygous insertion was found within intron 5. This segment was highly homologous to the Long INterspersed Element-1 (LINE-1) retrotranspozon. The spouse of J1 had normal alleles in both SLCO1B1 and SLCO1B3 genes, and their son was heterozygous for both alleles. Immunohistochemistry revealed that OATP1B1 and OATP1B3 proteins were not detectable in liver tissues from P1 and J1. The insertion of LINE-1 sequence within intron 5 of the Thymidylate synthase SLCO1B3 gene was found as heterozygotes with a frequency of 0.012 in Japanese. Thus, the predicted frequency of homozygotes was 0.00013. Conclusions. We found a novel genomic alteration causing Rotor syndrome in Japanese patients. The combination of the c.1738CÇT (p.R580X) mutation in the SLCO1B1 gene and the LINE-1 retrotranspozon insertion in the SLCO1B3 gene may be a haplotype specific for Japanese patients. Disclosures: The following people have nothing to disclose: Tatehiro Kagawa, Kazuya Anzai, Kota Tsuruya, Yoshitaka Arase, Shunji Hirose, Koichi Shiraishi, Tsuneo Kitamura, Yoshinao Kobayashi, Yoichi Hiasa, Tetsuya Mine Background and aims: Low bone turnover osteoporosis is common in patients with chronic cholestasis.