{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:46:43Z","timestamp":1783122403899,"version":"3.54.6"},"reference-count":47,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T00:00:00Z","timestamp":1663459200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Science Funds of China","award":["No.81600849"],"award-info":[{"award-number":["No.81600849"]}]},{"name":"National Science Funds of China","award":["No.82170919"],"award-info":[{"award-number":["No.82170919"]}]},{"name":"Major frontier issues of the application foundation project of Sichuan Science and Technology Department","award":["2020YJ0211"],"award-info":[{"award-number":["2020YJ0211"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The Cleft Palate Craniofacial Journal"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The role of MMP16 in lip development is unclear. This study aimed to identify nonsyndromic cleft lip with or without palate (NSCL\u2009\u00b1\u2009P) susceptible loci of MMP16 in western Han Chinese.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>We performed targeted sequencing around MMP16 combined with a 2-phase association analysis on common variants. Phase 2 association analysis was performed with NSCL\u2009\u00b1\u2009P specific subphenotypes (NSCL and NSCLP). Then we used rare variants burden analysis and genotyping, accompanied by motif analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>This study was completed in a tertiary medical center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients, Participants<\/jats:title>\n                    <jats:p>Phase 1 targeted sequencing included 159 patients with NSCL\u2009\u00b1\u2009P and 542 normal controls; phase 2 included 1626 patients with NSCL\u2009\u00b1\u2009P (1047 NSCL and 579 NSCLP) and 2255 normal controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Venous blood samples were collected from patients and used to extract DNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measures<\/jats:title>\n                    <jats:p>\n                      After Bonferroni correction, phase 1 significant threshold of p-value was 4.28\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      (0.05\/1167 single nucleotide polymorphisms [SNPs]), and phase 2 was .00025 (0.05\/200 SNPs). Burden analysis significant threshold p-value was .05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Common variants phase 1 association analysis identified 11 statistically significant SNPs (lowest p\u2009=\u20091.90\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      , odds ratio (OR)\u2009=\u20090.27, 95% CI: 0.17-0.44), phase 2 replication identified 16 SNPs in NSCL\u2009\u00b1\u2009P (lowest p\u2009=\u20096.26\u2009\u00d7\u200910\n                      <jats:sup>\u22126<\/jats:sup>\n                      , OR\u2009=\u20090.77, 95% CI: 0.69-0.86) and 9 in NSCL (lowest p\u2009=\u20098.44\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      , OR\u2009=\u20090.76, 95% CI: 0.66-0.87). Rare variants burden analysis showed no significant results, genotyping results showed they were maternally inherited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study identified MMP16 susceptible SNPs in NSCL\u2009\u00b1\u2009P and NSCL, emphasizing its potential role in lip development. Our study also highlighted the importance to perform association analysis with subphenotypes divided.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10556656221125392","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:51:21Z","timestamp":1663548681000},"page":"1625-1631","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>MMP16<\/i>\n                    as NSCL\u2009\u00b1\u2009P Susceptible Gene in Western Han Chinese"],"prefix":"10.1177","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0866-0893","authenticated-orcid":false,"given":"Yansong","family":"Lin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonglin","family":"Jia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,9,18]]},"reference":[{"key":"bibr1-10556656221125392","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24238"},{"key":"bibr2-10556656221125392","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60695-4"},{"key":"bibr3-10556656221125392","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195139068.001.0001","volume-title":"Cleft lip and palate: from origin to treatment","author":"Wyszynski 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