{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:31:41Z","timestamp":1790271101316,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T00:00:00Z","timestamp":1505433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Fifteen to twenty percent of alpha\u20101 antitrypsin deficiency patients (A1<jats:styled-content style=\"fixed-case\">ATD<\/jats:styled-content>) have a severe liver outcome (portal hypertension \u2010 <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>) during childhood. Since they all share the same <jats:styled-content style=\"fixed-case\">ZZ<\/jats:styled-content><jats:italic><jats:styled-content style=\"fixed-case\">SERPINA<\/jats:styled-content>1<\/jats:italic> genotype and that environmental factors such as alcohol cannot be advanced, the presence of modifier genes is now well recognized. <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s located on the <jats:italic><jats:styled-content style=\"fixed-case\">SERPINA<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">MAN<\/jats:styled-content>1B1<\/jats:italic> genes have already been tested in very few studies with contradictory or not replicated results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our genotype\u2013phenotype correlation study, performed on 92 <jats:styled-content style=\"fixed-case\">ZZ<\/jats:styled-content> children, aimed at determining once and for all if <jats:italic><jats:styled-content style=\"fixed-case\">SERPINA<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">MAN<\/jats:styled-content>1B1<\/jats:italic> polymorphisms may be implied in the onset of <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>. To do so, we also performed for the first time a complete haplotype reconstruction for data analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The two genetic associations with severe liver disease that had been suspected previously (one <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> for <jats:italic><jats:styled-content style=\"fixed-case\">SERPINA<\/jats:styled-content>1<\/jats:italic> and another for <jats:italic><jats:styled-content style=\"fixed-case\">MAN<\/jats:styled-content>1B1<\/jats:italic>) were not confirmed in our cohort. Moreover, the haplotype analysis identified only one major genetic background for the <jats:italic><jats:styled-content style=\"fixed-case\">SERPINA<\/jats:styled-content>1<\/jats:italic> Z\u2010allele, allowing us to exclude the presence of a frequent modifier <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> within. For <jats:italic><jats:styled-content style=\"fixed-case\">MAN<\/jats:styled-content>1B1<\/jats:italic>, four major haplotypes were identified but the prevalence of <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content> did not significantly differ between them.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that genetic polymorphisms in these two genes probably do not influence the onset of severe liver disease in A1<jats:styled-content style=\"fixed-case\">ATD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13586","type":"journal-article","created":{"date-parts":[[2017,9,9]],"date-time":"2017-09-09T01:16:41Z","timestamp":1504919801000},"page":"1608-1611","source":"Crossref","is-referenced-by-count":10,"title":["<i><scp>SERPINA<\/scp>1<\/i> and <i><scp>MAN<\/scp>1B1<\/i> polymorphisms are not linked to severe liver disease in a French cohort of alpha\u20101 antitrypsin deficiency children"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2351-9441","authenticated-orcid":false,"given":"Philippe","family":"Joly","sequence":"first","affiliation":[{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire Grand\u2010Est H\u00f4pital Edouard Herriot Hospices Civils de Lyon  Lyon France"},{"name":"Inter\u2010University Laboratory of Human Movement Science Univ Lyon \u2010 University Claude Bernard Lyon 1 \u2010 EA 7424  Villeurbanne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Lachaux","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lioara","family":"Restier","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhouaed","family":"Belmalih","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Hepatology and Nutrition Children's Hospital of Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Chapuis\u2010Cellier","sequence":"additional","affiliation":[{"name":"Laboratoire d'immunologie Centre Hospitalier Lyon\u2010Sud Hospices Civils de Lyon &amp; Universit\u00e9 Claude Bernard\u2010Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Francina","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire Grand\u2010Est H\u00f4pital Edouard Herriot Hospices Civils de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Renoux","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire Grand\u2010Est H\u00f4pital Edouard Herriot Hospices Civils de Lyon  Lyon France"},{"name":"Inter\u2010University Laboratory of Human Movement Science Univ Lyon \u2010 University Claude Bernard Lyon 1 \u2010 EA 7424  Villeurbanne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Bouchecareilh","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux\u2010Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires  Bordeaux France"},{"name":"France CNRS\u2010UMR5095 Bordeaux  Bordeaux Cedex France"},{"name":"INSERM UMR1053 Bordeaux Research In Translational Oncology Univ. Bordeaux BaRITOn  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66781-5"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1988.tb10767.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0216787"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000932"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21979"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22974"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23170"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.06.004"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/502802"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042409-151920"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.112.143487"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179369"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.13586","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.13586","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T14:48:40Z","timestamp":1695480520000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.13586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,15]]},"references-count":12,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1111\/liv.13586"],"URL":"https:\/\/doi.org\/10.1111\/liv.13586","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,15]]}}}