Zheng Ting-Ting, Liu Jia-He, Huang Wan-Tong, Hong Bo, Wang Di, Liu Chun-Yi, Zhang Jie, Li Si-Si, Wu Shao-Wei, Wang Qi, Chen Lei, Jin Lei
Department of Obstetrics and Gynecology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Department of Gynecology, Jinan Maternal and Child Care Hospital, Jinan 250000, Shandong Province, China.
World J Diabetes. 2025 May 15;16(5):103602. doi: 10.4239/wjd.v16.i5.103602.
There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus (GDM), and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.
To examine the association between single-nucleotide polymorphisms (SNPs) of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.
A nested case-control study was conducted with GDM cases ( = 412) and healthy controls ( = 412). DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience's MassARRAY gene mass spectrometry system. The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models. The generalized multi-factor dimensionality reduction (GMDR) method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.
The variation allele frequency of melatonin receptor 1B () rs10830963 was higher in the GDM group than in controls ( < 0.05). rs10830963 mutant G was associated with risk for GDM [adjusted odds ratio (aOR): 1.43; 95% confidence interval (95%CI): 1.13-1.80] in the additive model. rs10830963 GG + GC was significantly associated with the risk for GDM (aOR: 1.65; 95%CI: 1.23-2.22) in the dominant model. The two-locus model of rs10830963 and rs4721 was the best model ( < 0.05) for gene-gene interactions in the GMDR results. The high-risk rs10830963 × rs4721 type of interaction was a risk factor for GDM (aOR: 2.09; 95%CI: 1.49-2.93).
This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM. The G mutant allele of rs10830963 is identified as a risk factor for GDM in the additive model, and there may be gene-gene interactions between rs10830963 and rs4721. It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.
关于叶酸与妊娠期糖尿病（GDM）之间的潜在相关性存在相互矛盾的结果，叶酸代谢途径相关基因因素与GDM之间的相关性仍有待揭示。
研究叶酸代谢途径中酶基因的单核苷酸多态性（SNP）以及GDM相关基因与GDM发病风险之间的关联。
进行一项巢式病例对照研究，纳入GDM病例（n = 412）和健康对照（n = 412）。从血液样本中提取DNA，并使用Agena Bioscience公司的MassARRAY基因质谱系统对SNP进行基因分型。使用逻辑回归模型估计基因不同SNP与GDM发病风险之间的关联。使用GMDR 0.9软件，采用广义多因素降维（GMDR）方法分析基因-基因和基因-环境相互作用。
褪黑素受体1B（MTNR1B）rs10830963的变异等位基因频率在GDM组中高于对照组（P < 0.05）。在加性模型中，rs10830963突变型G与GDM发病风险相关[调整优势比（aOR）：1.43；95%置信区间（95%CI）：1.13 - 1.80]。在显性模型中，rs10830963 GG + GC与GDM发病风险显著相关（aOR：1.65；95%CI：1.23 - 2.22）。GMDR结果中，rs10830963和rs4721的两位点模型是基因-基因相互作用的最佳模型（P < 0.05）。高风险的rs10830963×rs4721相互作用类型是GDM的一个风险因素（aOR：2.09；95%CI：1.49 - 2.93）。
本研究未发现叶酸代谢酶SNP与GDM发病风险之间存在关联。rs10830963的G突变等位基因在加性模型中被确定为GDM的一个风险因素，且rs10830963与rs4721之间可能存在基因-基因相互作用。这有助于研究GDM的病因，并为该疾病的精准预防提供新的视角。
