State Key Laboratory of Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China.
Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, China.
Birth Defects Res. 2024 Oct;116(10):e2403. doi: 10.1002/bdr2.2403.
N6-methyladenosine (mA) is the most prevalent modification of RNA in eukaryotes which is associated with many cellular processes and diseases. Here, our objective is to explore whether genetic variants in mA modification genes are associated with the risk of non-syndrome orofacial clefts (NSOCs).
The transmission disequilibrium test (TDT) was performed to calculate the association between single nucleotide polymorphisms (SNPs) in mA modification genes and NSOCs risk in 944 case-parent trios. The function of SNP was predicted by HaploReg, RegulomeDB and histone enrichment data. The expression quantitative trait locus (eQTL) analysis was examined using Genotype-Tissue Expression (GTEx) and eQTLGen. The role of gene in the development of NSOCs was assessed with correlation and enrichment analysis based on gene expression data in mice craniofacial tissue and zebrafish embryo.
We identified that rs8078195 (A > C) in METTL16 was suggestively associated with the increased risk of NSOCs (OR = 1.32, p = 1.80E - 03). The region surrounding rs8078195 was subjected to deoxyribonuclease hypersensitivity and enriched with multiple histone modifications. In addition, it had a significant eQTL effect with METTL16 in skin tissue and human peripheral blood, which played an important role in NSOCs development. Bioinformatic analysis indicated that METTL16 contributed to the development of NSOCs probably by regulating cell cycle process.
Rs8078195 in METTL16 was associated with the occurrence of NSOCs.
N6-甲基腺苷（mA）是真核生物中最普遍的 RNA 修饰，与许多细胞过程和疾病有关。在这里，我们的目的是探索 mA 修饰基因中的遗传变异是否与非综合征性口面裂（NSOCs）的风险相关。
采用传递不平衡检验（TDT）计算 944 个病例-父母三体型中单核苷酸多态性（SNPs）与 NSOCs 风险之间的关联。通过 HaploReg、RegulomeDB 和组蛋白富集数据预测 SNP 的功能。使用基因型组织表达（GTEx）和 eQTLGen 进行表达数量性状基因座（eQTL）分析。基于小鼠颅面组织和斑马鱼胚胎的基因表达数据，通过相关性和富集分析评估基因在 NSOCs 发育中的作用。
我们发现 METTL16 中的 rs8078195（A>G）与 NSOCs 风险增加相关（OR=1.32，p=1.80E-03）。rs8078195 周围区域易受脱氧核糖核酸酶超敏反应影响，并富含多种组蛋白修饰。此外，它在皮肤组织和人外周血中与 METTL16 有显著的 eQTL 效应，在 NSOCs 发育中起重要作用。生物信息学分析表明，METTL16 可能通过调节细胞周期过程参与 NSOCs 的发生。
METTL16 中的 rs8078195 与 NSOCs 的发生有关。
