{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:43:58Z","timestamp":1785141838908,"version":"3.55.0"},"reference-count":82,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intrahepatic cholestasis of pregnancy (ICP) is characterized by the onset of pruritus and elevated serum transaminases and bile acids (BA). The key enzyme in BA synthesis is CYP7A1, and its functions are regulated by various nuclear receptors. The goal of this study is to evaluate the association between CYP7A1, NR1H1, RXRA, and PPARA gene variants and risk of ICP. Five single nucleotide variants (SNVs), rs3808607 (CYP7A1), rs56163822 (NR1H4), rs1800206 (PPARA), rs749759, and rs11381416 (NR2B1), were genotyped in a group of 96 ICP and 211 controls. The T allele of the CYP7A1 (rs3808607) variant may be a protective factor against ICP risk (OR = 0.697, 95% CI: 0.495\u20130.981, p = 0.038). Genetic model analysis showed that rs3808607 was associated with decreased risk of ICP under dominant (OR = 0.55, 95% CI: 0.32\u20133.16, p = 0.032, AIC = 380.9) and log-additive models (OR = 0.71, 95% CI: 0.51\u20131.00, p = 0.046, AIC = 381.4). The A insertion in the rs11381416 NR2B1 variant was associated with the degree of elevation in the liver function tests TBA (34.3 vs. 18.8 \u03bcmol\/L, p = 0.002), ALT (397.0 vs. 213.0 IU\/L, p = 0.017), and AST (186.0 vs. 114.4 IU\/L, p = 0.032) in ICP women. Results indicate an association between the CYP7A1 rs3808607 and the risk of ICP and the association of the rs11381416 of the NR2B1 receptor with higher values of liver function tests in women with ICP. A better understanding of the cooperation of proteins involved in BA metabolism may have important therapeutic implications in ICP and other hepatobiliary diseases.<\/jats:p>","DOI":"10.3390\/ijms26157456","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:56:16Z","timestamp":1754409376000},"page":"7456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Polymorphic Variants of Selected Genes Regulating Bile Acid Homeostasis in Women with Intrahepatic Cholestasis of Pregnancy"],"prefix":"10.3390","volume":"26","author":[{"given":"Krzysztof","family":"Pi\u0105tek","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, University of Zielona Gora, Licealna 9, 65-417 Zielona Gora, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8986-7772","authenticated-orcid":false,"given":"Gra\u017cyna","family":"Kurzawi\u0144ska","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Department of Perinatology, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2305-3116","authenticated-orcid":false,"given":"Marcin","family":"O\u017carowski","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants\u2014National Research Institute, Wojska Polskiego 71B, 60-630 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7919-5005","authenticated-orcid":false,"given":"Piotr J\u00f3zef","family":"Olbromski","sequence":"additional","affiliation":[{"name":"Clinic of Operational Gynecology, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kami\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, Independent Public Clinical Hospital No. 1, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2423-8238","authenticated-orcid":false,"given":"Maciej","family":"Br\u0105zert","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Treatment of Infertility, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6599-9204","authenticated-orcid":false,"given":"Tomasz M.","family":"Karpi\u0144ski","sequence":"additional","affiliation":[{"name":"Chair and Department of Medical Microbiology, Poznan University of Medical Sciences, Rokietnicka 10, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wies\u0142aw","family":"Markwitz","sequence":"additional","affiliation":[{"name":"Department of Perinatology, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Seremak-Mrozikiewicz","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Department of Perinatology, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland"},{"name":"Department of Perinatology, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Malarkiewicz, P., Nowacka, U., Januszaniec, A., Mankiewicz, A., Koz\u0142owski, S., and Issat, T. 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