Anh Le Kha, Niimi Teruyuki, Suzuki Satoshi, Hayakawa Toko, Kitagawa Ken, Sakuma Chisato, Imura Hideto, Kondo Hisataka, Tu Nguyen Huu, Son Tong Minh, Ngoc Vo Truong Nhu, Thao Tran Phuong, Duc Nguyen Minh, Loc Pham Nguyen Gia, Furukawa Hiroo, Natsume Nagana, Natsume Nagato
Division of Research and Treatment for Oral Maxillofacial Congenital Anomalies, Aichi Gakuin University, Nagoya 464-8651, Japan.
School of Dentistry, Hanoi Medical University, Hanoi 10000, Vietnam.
Genes (Basel). 2025 Jul 22;16(8):853. doi: 10.3390/genes16080853.
Non-syndromic orofacial clefts (NSOFCs) are one of the common congenital malformations in Vietnam, with 1.4 per 1000 live births, with notable sex differences in occurrence. This case-control study aims to investigate potential sex-specific interactions of and polymorphisms across NSOFC subtypes in a Vietnamese population.
A total of 720 participants were separated into 4 groups with a male/female ratio of 1:1 (160 individuals with cleft lip and palate (NSCLP), 160 with cleft lip only (NSCLO), 160 with cleft palate only (NSCPO), 240 healthy controls). Two single-nucleotide polymorphisms (SNPs), rs3809857 and rs227731, were genotyped by using the StepOnePlus Real-Time PCR System.
The most significant findings were found in the male NSCLO group under a recessive model of rs3809857 after applying Bonferroni correction, as a five-fold protective factor with OR = 0.18 (95% confidence interval: 0.05-0.64, = 0.0033). Additionally, the weak or moderate protective association between rs3809857 and male NSCLP was found with < 0.05 under the dominant model. However, there were no significant findings in the female NSOFC subtypes associated with . Conversely, rs227731 results showed a weak increased risk in female NSCLO and NSCPO with < 0.05.
this study identified the critical role of rs3809857 in reducing NSCLO risk in males. These findings support the potential influence of sex as a modifying factor in the genetic susceptibility to non-syndromic orofacial clefts.
非综合征性口腔颌面裂隙（NSOFCs）是越南常见的先天性畸形之一，每1000例活产中有1.4例，其发生率存在显著的性别差异。本病例对照研究旨在调查越南人群中NSOFC各亚型中 和 多态性潜在的性别特异性相互作用。
总共720名参与者被分为4组，男女比例为1:1（160例唇腭裂患者（NSCLP），160例仅唇裂患者（NSCLO），160例仅腭裂患者（NSCPO），240例健康对照）。使用StepOnePlus实时荧光定量PCR系统对两个单核苷酸多态性（SNP），即rs3809857和rs227731进行基因分型。
在应用Bonferroni校正后，在rs3809857的隐性模型下，男性NSCLO组发现了最显著的结果，作为一个五倍的保护因子，OR = 0.18（95%置信区间：0.05 - 0.64， = 0.0033）。此外，在显性模型下，rs3809857与男性NSCLP之间发现了弱或中度的保护关联， < 0.05。然而，与 相关的女性NSOFC亚型中没有显著发现。相反，rs227731的结果显示，女性NSCLO和NSCPO的风险略有增加， < 0.05。
本研究确定了rs3809857在降低男性NSCLO风险中的关键作用。这些发现支持了性别作为非综合征性口腔颌面裂隙遗传易感性的修饰因子的潜在影响。
