{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T23:06:08Z","timestamp":1778195168593,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T00:00:00Z","timestamp":1433376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Science Centre, Poland","award":["2012\/07\/B\/NZ2\/00115"],"award-info":[{"award-number":["2012\/07\/B\/NZ2\/00115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The locus on chromosome 15q13.3 containing GREM1 is correlated with the risk of nonsyndromic cleft lip with or without cleft palate (NSCL\/P). The aim of the present study was to find the <jats:italic>GREM1<\/jats:italic> functional variants implicated in the aetiology of this common developmental anomaly in the Polish population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight polymorphisms were genotyped in 334 NSCL\/P patients and 955 controls. In addition, the <jats:italic>GREM1<\/jats:italic> protein\u2010coding region was sequenced in 96 NSCL\/P patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant association with a risk of oral clefts was found for 5 tested polymorphisms. The lowest p<jats:sub>trend<\/jats:sub> values were identified for rs16969681, rs16969816, and rs1258763 (p<jats:sub>trend<\/jats:sub> 4.09E\u201005, 3.35E\u201005, and 0.0002, respectively). The putative functional variant rs16969681, located in a region that has enhancer activity, was associated with a 2.6\u2010fold lower risk for NSCL\/P (odds ratio [OR]\u2009=\u20090.38; 95% confidence interval [CI], 0.24\u20130.61, <jats:italic>p<\/jats:italic>\u2009=\u20092.37E\u201005). The previously reported association of rs1258763 with NSCL\/P was replicated (OR\u2009=\u20090.57; 95% CI, 0.44\u20130.73; <jats:italic>p<\/jats:italic>\u2009=\u20091.10E\u201005). For all tested <jats:italic>GREM1<\/jats:italic> variants, no significant sex\u2010by\u2010genotype interaction effects were observed. The sequencing analysis did not detect any rare variants implicated in the development of oral clefts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results might suggest that variants influencing <jats:italic>GREM1<\/jats:italic> expression levels, rather than variants affecting the function of the encoded protein, are significant factors in NSCL\/P etiology. Birth Defects Research (Part A) 103:847\u2013856, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23391","type":"journal-article","created":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T16:36:53Z","timestamp":1433435813000},"page":"847-856","source":"Crossref","is-referenced-by-count":11,"title":["Association between polymorphisms at the <i>GREM1<\/i> locus and the risk of nonsyndromic cleft lip with or without cleft palate in the Polish population"],"prefix":"10.1002","volume":"103","author":[{"given":"Adrianna","family":"Mostowska","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Poznan University of Medical Sciences Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamil K.","family":"Hozyasz","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Institute of Mother and Child Warsaw 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Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Zadurska","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Institute of Dentistry, The Medical University of Warsaw  Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Radomska","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Institute of Dentistry, The Medical University of Warsaw  Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabela","family":"Dunin\u2010Wilczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Jaw Orthopaedics Medical University of Lublin Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142 P.","family":"Jagodzi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Poznan University of Medical Sciences Poznan 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