{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:48:01Z","timestamp":1761630481186,"version":"3.30.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2556,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>\n                                 <jats:bold>Primary biliary cirrhosis (PBC) is a multifactorial disease in which genetic factors rather than environmental factors may predominantly contribute to the pathogenesis. In order to identify the genetic determinants of the disease severity and progression of PBC, we examined an association of seven tag single-nucleotide polymorphisms (SNPs) in the multidrug resistance protein 3 (<\/jats:bold>\n                                 <jats:bold>\n                                    MDR3\/ABCB4\n                                 <\/jats:bold>\n                                 <jats:bold>) gene in 148 Japanese PBC patients and 150 age- and sex-matched healthy control subjects. SNPs were detected via polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR direct DNA sequencing methods. Subsequently, haplotypes were constructed from three tag SNPs (rs31658, rs31672, and rs1149222) that were significantly associated with progression of PBC. Logistic regression analyses revealed that a Hap 2 haplotype and its homozygous diplotype, Hap 2\/Hap 2, in<\/jats:bold>\n                                 <jats:bold>\n                                    MDR3\n                                 <\/jats:bold>\n                                 <jats:bold>were closely associated with the susceptibility to jaundice-type progression of PBC [<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.004, odds ratio (OR) 3.93, 95% confidence interval (CI) 1.56\u20139.90 and<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.0003, OR 17.73, 95% CI 3.77\u201383.42, respectively]. Conversely, another haplotype, Hap 1, and its homozygous diplotype, Hap 1\/Hap 1, were associated with the insusceptibility to the progression to late-stage PBC (<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.021, OR 0.55, 95% CI 0.33\u20130.91 and<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.011, OR 0.24, 95% CI 0.08\u20130.71, respectively).<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>The present study is the first report of an association of<\/jats:bold>\n                                 <jats:bold>\n                                    MDR3\n                                 <\/jats:bold>\n                                 <jats:bold>haplotypes and diplotypes with progression of PBC. The Hap 2\/Hap 2 diplotype in<\/jats:bold>\n                                 <jats:bold>\n                                    MDR3\n                                 <\/jats:bold>\n                                 <jats:bold>could therefore be potentially applied to DNA-based diagnosis in Japanese patients with PBC as a strong genetic biomarker for predicting the progression and prognosis of PBC. (Hepatology 2008.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.22382","type":"journal-article","created":{"date-parts":[[2008,4,18]],"date-time":"2008-04-18T20:16:32Z","timestamp":1208549792000},"page":"853-862","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":28,"title":["Single-nucleotide polymorphism analysis of the multidrug resistance protein 3 gene for the detection of clinical progression in Japanese patients with primary biliary cirrhosis"],"prefix":"10.1097","volume":"48","author":[{"given":"Yuki","family":"Ohishi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Iio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Higa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mao","family":"Inayoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Aiba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsumasa","family":"Komori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuhisa","family":"Omagari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Ishibashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Tsukamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-18-20241202","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1056\/NEJM199611213352107","article-title":"Primary 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