{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:47:58Z","timestamp":1767340078574,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research","award":["19K10325","20K10106","21K17194"],"award-info":[{"award-number":["19K10325","20K10106","21K17194"]}]},{"name":"Grant-in-Aid for Young Scientists","award":["19K10325","20K10106","21K17194"],"award-info":[{"award-number":["19K10325","20K10106","21K17194"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>This study aims to identify potential variants in the TP63\u2013IRF6 pathway and GREM1 for the etiology of non-syndromic orofacial cleft (NSOFC) among the Vietnamese population. By collecting 527 case\u2013parent trios and 527 control samples, we conducted a stratified analysis based on different NSOFC phenotypes, using allelic, dominant, recessive and over-dominant models for case\u2013control analyses, and family-based association tests for case\u2013parent trios. Haplotype and linkage disequilibrium analyses were also conducted. IRF6 rs2235375 showed a significant association with an increased risk for non-syndromic cleft lip and palate (NSCLP) and cleft lip with or without cleft palate (NSCL\/P) in the G allele, with pallele values of 0.0018 and 0.0003, respectively. Due to the recessive model (p = 0.0011) for the NSCL\/P group, the reduced frequency of the GG genotype of rs2235375 was associated with a protective effect against NSCL\/P. Additionally, offspring who inherited the G allele at rs2235375 had a 1.34-fold increased risk of NSCL\/P compared to the C allele holders. IRF6 rs846810 and a G-G haplotype at rs2235375\u2013rs846810 of IRF6 impacted NSCL\/P, with p-values of 0.0015 and 0.0003, respectively. In conclusion, our study provided additional evidence for the association of IRF6 rs2235375 with NSCLP and NSCL\/P. We also identified IRF6 rs846810 as a novel marker associated with NSCL\/P, and haplotypes G-G and C-A at rs2235375\u2013rs846810 of IRF6 associated with NSOFC.<\/jats:p>","DOI":"10.3390\/genes14111995","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T09:54:08Z","timestamp":1698227648000},"page":"1995","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case\u2013Control and Family-Based Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Loc Nguyen Gia","family":"Pham","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":"Odonto-Maxillo Facial Hospital of Ho Chi Minh City, 263-265 Tran Hung Dao Street, District 1, Ho Chi Minh City 71000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minh Duc","family":"Nguyen","sequence":"additional","affiliation":[{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linh Cao Hoai","family":"Nguyen","sequence":"additional","affiliation":[{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuan Duc","family":"Nguyen","sequence":"additional","affiliation":[{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kien Ai","family":"Hoang","sequence":"additional","affiliation":[{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duc Minh","family":"Nguyen","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 Odonto-Stomatology, Hanoi Medical University, Hanoi 10000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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"},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toko","family":"Hayakawa","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makino","family":"Hiyori","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroo","family":"Furukawa","sequence":"additional","affiliation":[{"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":[{"role":"author","vocabulary":"crossref"}]},{"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 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