Correlation of Folic Acid Metabolic Gene Polymorphisms, Homocysteine, Vitamin B12, and Red Blood Cell Folate with Adverse Pregnancy Outcomes
文献来源：Altern Ther Health Med. 2023 Nov 3:AT9258.
作者:Zhao X, Yang L, Wang M, Zhang X
作者单位：Department of Obstetrics, Qingdao Central Hospital, Qingdao, Shandong, China.
研究目的
本研究旨在探讨叶酸(FA)代谢基因多态性、同型半胱氨酸(Hcy)、维生素B12(VitB12)和红细胞叶酸(RBCF)与不良妊娠结局（APO）的关系。本研究结果对今后不良妊娠的预防和治疗有一定的帮助。
研究方法
选取2020年8月~2022年10月青岛市中心医院收治的118例孕妇进行回顾性分析，其中正常分娩62例(对照组，CG)，不良妊娠56例(研究组，RG)。在两个队列中检测MTHFRC677T、MTHFRA1298C和MTRRA66G基因位点的单核苷酸多态性。此外，观察研究组不同基因型携带者Hcy、VitB12、RBCF水平的差异，以及Hcy、VitB12、RBCF的变化。
研究结果
临床特点及指标比较
RG和CG在临床上具有可比性，因为她们在年龄、体重指数（BMI)、妊娠三个月和孕酮值方面没有明显差异（P>0.05，表1）。
MTHFRC677T基因型与等位基因频率分布的比较
MTHFRC677T基因分型结果显示，RG中TT基因型的比例为28.57%，高于CG(P<0.05);CC和CT基因型比例组间比较差异无统计学意义(P＞0.05)。等位基因频率检测结果显示，RG中T基因的比例高于CG(P<0.05，表2)。
MTHFRA1298C基因型与等位基因频率分布的比较
A1298C基因分型结果显示AA、AC、CC基因型比例及A、C等位基因频率组间差异均无统计学意义(P＞0.05，表3)。
MTRRA66G基因型与等位基因频率分布的比较
A66G基因分型检测发现RG与CG之间存在统计学意义(P<0.05)，RG中MTRR66AG基因携带者比例明显低于CG(P<0.05)，66GG基因携带者比例明显高于CG(P<0.05)。等位基因频率检测也显示RG中A基因的比例较低，G基因的比例较高(P<0.05，表4)。
不良妊娠结局的多因素分析
以孕妇不良妊娠(伴/未伴)为终点，对上述基因多态性差异进行Logistic回归分析。MTHFR677TT和MTRR66GG基因型携带者的不良妊娠风险分别增加约3.5倍和2.6倍(P<0.05)，MTRR66AG基因型携带者的不良妊娠风险降低(P<0.05，表5)。
Hcy、VitB12和RBCF的比较
进一步检测Hcy、VitB12和RBCF水平，发现RG中Hcy、VitB12和RBCF水平分别为(8.02±1.38)μmol/L、(517.65±30.27)pg/mL和(1715.73±258.70)nmol/L，与CG相比，Hcy水平较高，VitB12和RBCF水平较低(P<0.05，图1)。
MTHFRC677T与Hcy、VitB12和RBCF的相关性
比较不同MTHFRC677T基因型孕妇RG中Hcy、VitB12和RBCF水平，可以看出，Hcy、VitB12和RBCF在677CC和677CT基因携带者之间无差异(P＞0.05);而677T基因携带者的Hcy水平高于其他两种基因型，VitB12和RBCF水平低于其他两种基因型(P<0.05，图2)。
A:MTHFRCC、CT和TT基因型孕妇Hcy的比较；B:MTHFRCC、CT和TT基因型孕妇维生素B12的比较；C:MTHFRCC、CT和TT基因型孕妇的RBCF比较。
MTRRA66G、Hcy、VitB12与RBCF的相关性
在不同MTRRA66G基因携带者中，66GG基因携带者Hcy最高，66AG基因携带者Hcy最低(P<0.05)。VitB12和RBCF则相反，即66GG基因携带者的VitB12和RBCF水平最低，66AG基因携带者的VitB12和RBCF水平最高(P<0.05，图3)。
结论
MTHFR 677TT和MTRR 66GG携带者Hcy水平升高，Vit B12和RBCF降低，不良妊娠风险增加，而MTRR 66AG携带者风险降低。未来可通过检测母体FA代谢基因多态性、Hcy、Vit B12、RBCF来评估不良妊娠结局（APO）的风险，制定有效、准确的针对性治疗方案，确保孕妇正常分娩和新生儿健康。
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