Beijing Municipal Key Laboratory of Child Development and Nutriomics, Translational Medicine Laboratory, Capital Institute of Pediatrics, Beijing, 100020, China.
Reprod Sci. 2023 May;30(5):1585-1593. doi: 10.1007/s43032-022-01116-5. Epub 2022 Nov 2.
Inositol is closely related to the occurrence of neural tube defects (NTDs). Inositol 1, 3, 4-trisphosphate 5/6-kinase (ITPK1) gene encoded an essential regulatory enzyme ITPK1, which is involved in inositol metabolism and has a critical role in the development of neural tube and axial mesoderm. It had been reported that some polymorphisms of critical genes in inositol pathways, including ITPK1, were associated with NTDs in Chinese pregnant women; however, the association between fetus ITPK1 polymorphisms and NTDs had not been reported. In a high incidence of NTDs region of China, a case-control study was performed to evaluate the association between fetal ITPK1 polymorphisms and NTDs. The ITPK1 polymorphisms were genotyped by iPLEX® Gold assay. Inositol levels in fetus brain tissues were analyzed. Three genetic polymorphisms of fetus ITPK1's, including rs3818175, rs2295394, and rs4586354, were statistically associated with spina bifida (NTD subtypes). A higher risk of spina bifida was associated with genotype GG of rs3818175, genotype CC of rs4586354, and genotype TT of rs2295394 (OR = 2.66, 95% CI [1.17-6.05], P = 0.017; OR = 2.22, 95% CI [1.02-4.80], P = 0.041; and OR = 2.33, 95% CI [1.00-5.48], P = 0.047), when compared with the other wild-type genotypes CC, TT, and CC, respectively. Decreased brain inositol level was found in NTDs fetuses, compared to normal controls. Inositol levels were found to significantly decrease with rs2295394 (CC genotype), rs4586354 (TT genotype), and rs3818175 (GC genotype) (P < 0.05). The polymorphisms of fetus ITPK1 were associated with the incidence of NTDs and might be a genetic risk factor for spina bifida.
肌醇与神经管缺陷（NTDs）的发生密切相关。肌醇 1,3,4-三磷酸 5/6-激酶（ITPK1）基因编码一种必需的调节酶 ITPK1，它参与肌醇代谢，在神经管和轴中胚层的发育中起着关键作用。已有报道称，肌醇途径中的一些关键基因（包括 ITPK1）的多态性与中国孕妇的 NTDs 有关；然而，胎儿 ITPK1 多态性与 NTDs 之间的关系尚未报道。在我国 NTDs 高发地区，进行了一项病例对照研究，以评估胎儿 ITPK1 多态性与 NTDs 的关系。通过 iPLEX® Gold assay 对 ITPK1 多态性进行基因分型。分析了胎儿脑组织中的肌醇水平。胎儿 ITPK1 的三个遗传多态性，包括 rs3818175、rs2295394 和 rs4586354，与脊柱裂（NTD 亚型）呈统计学相关。rs3818175 的 GG 基因型、rs4586354 的 CC 基因型和 rs2295394 的 TT 基因型与脊柱裂的高风险相关（OR=2.66，95%CI[1.17-6.05]，P=0.017；OR=2.22，95%CI[1.02-4.80]，P=0.041；OR=2.33，95%CI[1.00-5.48]，P=0.047），与其他野生型基因型 CC、TT 和 CC 相比。与正常对照组相比，NTDs 胎儿的大脑中肌醇水平降低。发现肌醇水平随着 rs2295394（CC 基因型）、rs4586354（TT 基因型）和 rs3818175（GC 基因型）的变化而显著降低（P<0.05）。胎儿 ITPK1 的多态性与 NTDs 的发生率有关，可能是脊柱裂的遗传危险因素。
