探讨正常孕妇妊娠期血清同型半胱氨酸(Hcy)浓度与MTHFR基因C677T位点多态性及红细胞叶酸(RBCF)水平的相关性。

选择2018年1月至2019年4月，在眉山市妇幼保健院进行常规产前检查的483例早孕期正常孕妇为研究对象。根据其MTHFR基因C677T位点的CC、CT与TT基因型，将其分为CC组、CT组与TT组。采用荧光定量PCR法，检测受试者MTHFR基因C677T位点多态性；采用循环酶法、电化学发光法，分别检测受试者早、中、晚孕期血清Hcy浓度与RBCF水平。对3组受试者早、中、晚孕期的血清Hcy浓度与RBCF水平进行比较，采用单因素方差分析，而二者的相关性分析，采用直线回归分析。3组受试者年龄、孕龄、孕次、产次等一般临床资料比较，差异均无统计学意义(P>0.05)。本研究遵循的程序符合《世界医学协会赫尔辛基宣言》要求，与所有受试者签署临床研究知情同意书。

①这483例受试者的MTHFR基因C677T位点的CC、CT、TT基因型，分别为159例、237例、87例，分别纳入CC组、CT组与TT组；其基因型表达频率分别为32.9%、49.1%与18.0%；C、T等位基因频率分别为57.5%与42.5%。②483例受试者早、中、晚孕期血清Hcy浓度分别为(5.2±2.4)、(3.8±2.0)、(4.8±2.5) μmol/L，RBCF水平分别为(965±190)、(1 157±189)、(1 179±225) ng/mL，早、中、晚孕期血清Hcy浓度、RBCF水平分别比较，差异均有统计学意义(F＝44.542、163.830，P<0.001)。CC组、CT组、TT组受试者早孕期血清Hcy浓度及早、中、晚孕期RBCF水平分别比较，差异均有统计学意义(F＝8.925、9.181、19.757、21.877，P<0.001)。③直线回归分析结果显示，483例受试者早、中、晚孕期血清Hcy浓度与其RBCF水平呈线性负相关关系，建立的直线回归方程为y＝－0.003x＋7.986(R²＝0.082，F＝129.669，P<0.001)，其中，x为RBCF水平(ng/mL)，y为血清Hcy浓度(μmol/L)。

正常孕妇妊娠期血清Hcy浓度与MTHFR基因C677T位点多态性及RBCF水平相关。对育龄女性进行MTHFR基因C677T位点多态性筛查、血清Hcy浓度和RBCF水平监测，对围孕期保健具有重要指导意义。

To investigate correlations between serum homocysteine (Hcy) concentration at different trimesters of pregnancy and C677T polymorphism of MTHFR gene and red blood cell folate (RBCF) level of pregnant women.

From January 2018 to April 2019, a total of 483 healthy pregnant women in the first trimester who received regular prenatal examinations in Meishan Maternal and Child Health Hospital were selected as research subjects. According to detection results of C677T polymorphism of MTHFR gene, the subjects were divided into CC group, CT group and TT group with genotypes of CC, CT and TT, respectively. Fluorescent quantitative PCR method was used to detect C677T polymorphism of MTHFR gene in all subjects; cyclophorase method and electrochemiluminescence method were used to detect serum Hcy concentrations and RBCF levels in the first, second and third trimester of all subjects. One-way ANOVA method was used to compare serum Hcy concentrations and RBCF levels among three groups of subjects in the first, second and third trimester. The correlation between them was analyzed by linear regression method. There were no statistically significant differences in the general clinical data of three groups, such as age, gestational age, gravidity and parity (P>0.05). This study was in line with World Medical Association Declaration of Helsinki revised in 2013, and informed consent for clinical research was signed with each subject.

①Among the 483 cases of subjects, there were 159 cases, 237 cases and 87 cases of CC, CT and TT genotypes of C677T polymorphism of MTHFR gene respectively, and the frequencies of these three genotypes were 32.9%, 49.1% and 18.0%, respectively, and the frequencies of C and T alleles were 57.5% and 42.5%, respectively. ②Serum Hcy concentrations of the 483 subjects in the first, second and third trimester were (5.2±2.4) μmol/L, (3.8±2.0) μmol/L and (4.8±2.5) μmol/L, respectively, and RBCF levels were (965±190) ng/mL and (1 157±189) ng/mL, (1 179±225) ng/mL, respectively, and there were statistically significant differences in serum Hcy concentrations and RBCF levels of all subjects in the first, second and third trimester (F=44.542, 163.830; P<0.001). The serum Hcy concentrations in the first trimester and RBCF levels in the first, second and third trimester of CC group, CT group and TT group were compared, and all the differences were statistically significant (F=8.925, 9.181, 19.757, 21.877; P<0.001). ③Result of linear regression analysis showed that serum Hcy concentrations of the 483 subjects in the first, second and third trimester had a linear negative correlation with their RBCF levels. The established linear regression equation was y=-0.003x+ 7.986 (R²=0.082, F=129.669, P<0.001), and x referred to RBCF level (ng/mL), y referred to serum Hcy concentration (μmol/L).

The serum Hcy concentration of normal pregnant woman is related with C677T polymorphism of MTHFR gene and RBCF level. Screening C677T polymorphism of MTHFR gene, monitoring serum Hcy concentrations and RBCF levels for women of childbearing age has important guiding significance for perinatal care.