Thao Tran Phuong, Niimi Teruyuki, Suzuki Satoshi, Hayakawa Toko, Sakuma Chisato, Kitagawa Ken, Imura Hideto, Kondo Hisataka, Tu Nguyen Huu, Son Tong Minh, Ngoc Vo Truong Nhu, Anh Le Kha, Loc Pham Nguyen Gia, Furukawa Hiroo, Natsume Nagana, Natsume Nagato
Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan.
School of Dentistry, Hanoi Medical University, Hanoi 10000, Vietnam.
Genes (Basel). 2025 Jul 24;16(8):862. doi: 10.3390/genes16080862.
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 , , and genes for association with NSCL/P in a Japanese cohort. A case-control 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 (), rs13041247 (), and rs3809857 () using TaqMan assays. Associations were assessed using chi-squared tests, with results stratified by sex and corrected for multiple comparisons using the Bonferroni method. The rs7078160 A allele was significantly associated with an increased risk for NSCL/P (OR = 1.67, < 0.00001). The association was particularly strong in females (OR = 1.93, < 0.00001) but not significant in males after correction. The rs13041247 variant showed a nominal protective association with the NSCLO subtype that was not significant after Bonferroni correction. No significant association was found for . A notable gene-gene interaction was observed, where carrying risk alleles for both and significantly increased overall NSCL/P risk (OR = 2.65, = 0.00008). rs7078160 is a significant risk factor for NSCL/P in the Japanese population, with a pronounced female-specific effect. A synergistic interaction between and elevates disease risk, whereas was not implicated in this cohort. These findings underscore the population-specific genetic architecture of NSCL/P.
非综合征性唇裂伴或不伴腭裂（NSCL/P）是一种常见的多因素先天性异常。由于基因关联可能具有人群特异性，本研究旨在调查日本队列中、和基因的单核苷酸多态性（SNP）与NSCL/P的关联。进行了一项病例对照研究，纳入了310名来自爱知学院牙科医院的日本NSCL/P患者和308名种族匹配的健康对照。我们使用TaqMan分析对SNP rs7078160（）、rs13041247（）和rs3809857（）进行基因分型。使用卡方检验评估关联，结果按性别分层，并使用Bonferroni方法对多重比较进行校正。rs7078160 A等位基因与NSCL/P风险增加显著相关（OR = 1.67，< 0.00001）。这种关联在女性中尤为强烈（OR = 1.93，< 0.00001），但校正后在男性中不显著。rs13041247变异与NSCLO亚型存在名义上的保护关联，经Bonferroni校正后不显著。未发现与有显著关联。观察到一个显著的基因-基因相互作用，即同时携带和的风险等位基因会显著增加总体NSCL/P风险（OR = 2.65，= 0.00008）。rs7078160是日本人群中NSCL/P的一个显著风险因素，具有明显的女性特异性效应。和之间的协同相互作用会增加疾病风险，而在该队列中未涉及。这些发现强调了NSCL/P人群特异性的遗传结构。
