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)基因编码必需的调节酶ITPK1,该酶参与肌醇代谢,并在神经管和中胚层的发育中起关键作用。据报道,肌醇通路中一些关键基因的多态性,包括ITPK1在内,与中国孕妇的NTDs相关;然而,胎儿ITPK1多态性与NTDs之间的关联尚未报道.在我国NTDs高发地区,我们进行了一项病例对照研究,以评估胎儿ITPK1多态性与NTDs之间的关联.通过iPLEX®Gold测定对ITPK1多态性进行基因分型。分析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,在统计学上与脊柱裂(NTD亚型)相关.脊柱裂的风险较高与rs3818175的基因型GG,rs4586354的基因型CC和rs2295394的基因型TT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相比,TT,CC,分别。在NTDs胎儿中发现脑肌醇水平降低,与正常对照相比。发现肌醇水平显着降低与rs2295394(CC基因型),rs4586354(TT基因型),rs3818175(GC基因型)(P<0.05)。胎儿ITPK1基因多态性与NTDs的发生有关,可能是脊柱裂的遗传危险因素。
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.