{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:59:57Z","timestamp":1785416397942,"version":"3.56.0"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["23K09325"],"award-info":[{"award-number":["23K09325"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Non-syndromic cleft lip with or without palate (NSCL\/P) is a common, multifactorial congenital anomaly. As genetic associations can be population-specific, this study aimed to investigate single-nucleotide polymorphisms (SNPs) in the VAX1, MAFB, and WNT3 genes for association with NSCL\/P in a Japanese cohort. Methods: A case\u2013control study was conducted with 310 Japanese patients with NSCL\/P and 308 ethnically matched healthy controls from Aichi Gakuin Dental Hospital. We genotyped SNPs rs7078160 (VAX1), rs13041247 (MAFB), and rs3809857 (WNT3) using TaqMan assays. Associations were assessed using chi-squared tests, with results stratified by sex and corrected for multiple comparisons using the Bonferroni method. Results: The VAX1 rs7078160 A allele was significantly associated with an increased risk for NSCL\/P (OR = 1.67, p &lt; 0.00001). The association was particularly strong in females (OR = 1.93, p &lt; 0.00001) but not significant in males after correction. The MAFB rs13041247 variant showed a nominal protective association with the NSCLO subtype that was not significant after Bonferroni correction. No significant association was found for WNT3. A notable gene\u2013gene interaction was observed, where carrying risk alleles for both VAX1 and MAFB significantly increased overall NSCL\/P risk (OR = 2.65, p = 0.00008). Conclusions:\u00a0VAX1 rs7078160 is a significant risk factor for NSCL\/P in the Japanese population, with a pronounced female-specific effect. A synergistic interaction between VAX1 and MAFB elevates disease risk, whereas WNT3 was not implicated in this cohort. These findings underscore the population-specific genetic architecture of NSCL\/P.<\/jats:p>","DOI":"10.3390\/genes16080862","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T09:05:12Z","timestamp":1753347912000},"page":"862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of VAX1, MAFB, WNT3 with Non-Syndromic Cleft Lip with or without Cleft Palate in a Japanese Population"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9027-5322","authenticated-orcid":false,"given":"Tran Phuong","family":"Thao","sequence":"first","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"School of Dentistry, Hanoi Medical University, Hanoi 10000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3007-0686","authenticated-orcid":false,"given":"Teruyuki","family":"Niimi","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Cleft Lip and Palate Center, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Division of Speech, Hearing, and Language, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-1356","authenticated-orcid":false,"given":"Toko","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Cleft Lip and Palate Center, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Sakuma","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Imura","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Cleft Lip and Palate Center, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Division of Speech, Hearing, and Language, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7373-9282","authenticated-orcid":false,"given":"Hisataka","family":"Kondo","sequence":"additional","affiliation":[{"name":"Junior College, Aichi Gakuin University, Nagoya 464-0037, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Huu","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia\u2014Resuscitation, Hanoi Medical University, Hanoi 10000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong Minh","family":"Son","sequence":"additional","affiliation":[{"name":"School of Dentistry, Hanoi Medical University, Hanoi 10000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vo Truong Nhu","family":"Ngoc","sequence":"additional","affiliation":[{"name":"School of Dentistry, Hanoi Medical University, Hanoi 10000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7872-9291","authenticated-orcid":false,"given":"Le Kha","family":"Anh","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"School of Dentistry, Hanoi Medical University, Hanoi 10000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pham Nguyen Gia","family":"Loc","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Odonto-Maxillo Facial Hospital of Ho Chi Minh City, 263-265 Tran Hung Dao Street, District 1, Ho Chi Minh City 71000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroo","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Division of Speech, Hearing, and Language, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagana","family":"Natsume","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Cleft Lip and Palate Center, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Division of Speech, Hearing, and Language, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7943-2284","authenticated-orcid":false,"given":"Nagato","family":"Natsume","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2\u201311 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Cleft Lip and Palate Center, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"},{"name":"Division of Speech, Hearing, and Language, Aichi Gakuin Dental Hospital, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1597\/05-167","article-title":"Asian Oral-Facial Cleft Birth Prevalence","volume":"43","author":"Cooper","year":"2006","journal-title":"Cleft Palate Craniofac. 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