育龄妇女叶酸代谢通路关键酶基因多态性对血浆同型半胱氨酸水平的影响

An association study between gene polymorphism of the key enzyme＇s folacin metabolism pathway and plasmatic homocysteine levels in fertile woman

目的观察育龄妇女叶酸代谢通路关键酶基因多态性对血浆同型半胱氨酸水平的影响。方法2012年通过整群抽样方法抽取535名江苏省绍兴市年龄为20-45岁之间的育龄妇女，平均年龄为28．2（95％CI：27．8～28．6）岁。抽取静脉血5ml，加入抗凝剂EDTA或柠檬酸钠连续采集样本7d，共采集1465名调查对象血样，分离血细胞后，采用离心柱法进行DNA提取。然后对采集到的样本进行叶酸代谢关键酶基因多态性检测及血浆同型半胱氨酸（homocysteine，Hcy）水平分析，分析不同位点基因型的Hey差异。结果共检测了调查对象MTHFR、MS、MSR和CBS基因上的8个单核苷酸多态性（SNP）位点。MTHFR基因上的rs1801131位点基因型AA的Hcy平均浓度（8．99μmol／L）高于CC（7．81μmol／L）及CA（8．38μmol／L）型，P〈0．01。MTHFR基因上的rs1801133基因型为TT的调查对象Hcy平均浓度（11．10μmol／L）高于CC（8．15μmoL／L）及CT（8．45μmol／L）型，P〈0．01。该两个位点的基因型组合AA—TT会导致Hcy浓度的升高（11．02μmol／L），均高于其他基因型组合，特别是CC—CC基因型组合（7．83μmol／L），风险系数是该基因型的1．41（95％CI：1．20—1．66）倍。结论MTHFR基因上的rs1801131和rs1801133的基因突变可导致Hcy水平升高。

Objective The effect of the gene polymorphism for the key enzyme＇s folacin metabolism pathway on plasmatic homocysteine （Hcy） levels in fertile woman was observed. Methods The subjects were from Shaoxing City, Jiangsu province in 2012, the selection criteria for the women of childbearing age were between 20-45 years old, with an average age of 28.2 （95% CI： 27.8-28.6） years old. Sample collection continued uninterrupted lasted seven days, a total of 535 samples were collected, venous blood with EDTA addition or sodium citrate to anticoagulant. After separation, the blood cells and blood plasma were cryopreserved. DNA was extracted using spin column method. All the samples were selected for the gene polymorphism testing of the key enzyme＇s on folate metabolism and monitoring of plasmatic Hcy level. Results Eight single nucleotide polymorphism （SNP） sites of methylenetetrahydrofolate reductase gene （MTHFR）, methionine synthase gene（MS） , synthetic methionine reductase gene（MSR） and cystathionine synthase gene （CBS） were detected. It was found the genotype AA of the SNP sites-rs 1801131 would result higher plasmatic Hey levels （8.99μmol/L） than the genotypes CC （7. 81 μmoL/L） and CA（8. 38 μmol/L） （P 〈 0. 01 ）. Similarly, the genotype TT of the SNP sites-rs1801133 was significantly responded to the increasing of Hey levels （ 11.10 μmol/L） than the genotype CC （8. 15 μmol/L） and CT （8.45 μmol/L）, （P 〈 0.01 ）. The two sites of genotype combination of AA-TF could also result in the significant increase of Hey levels （11.02 μmol/L） than other combined genotypes （genotypes CC-CC, CA-CC, CA-CT, AA-CC, AA-CT） , especially the genotype CC-CC. And the risk factor was 1.41 （95CI：1.20-1.66 ） times over the genotype CC-CC. Conclusion The gene mutations of two SNP sites rs1801131 and rs1801133 in MTHFR would increase Hcy levels.