亚甲基四氢叶酸还原酶基因677位多态性、高同型半胱氨酸血症与复发性流产

Association of C677T Methylenetetrahy Hydrofolate Reductase(MTHFR) Polymorphism and Homocysteine with Recurrent Pregnancy Loss

目的:探讨亚甲基四氢叶酸还原酶基因(MTHFR)多态性(C677T)与高同型半胱氨酸(Hcy)血症以及复发性流产之间的关系。方法:采用前瞻性病例对照研究方法,收集71例复发性自然流产患者为病例组,另征集同期58例有正常妊娠史者为对照组,利用PCR-RFLP方法研究MTHFR基因多态性(C677T);同时应用酶法测定血清同型半胱氨酸水平;并随访病例组的妊娠结局。结果:①MTHFR基因677位点的3种基因型在病例组和对照组分布分别为CC:14.1%vs 43.1%、CT:49.3%vs 25.9%、TT:36.6%vs 31.0%,组间比较有极显著统计学差异(χ2=14.7,df=2,P=0.001);其中CC基因型在病例组显著降低(P=0.000,OR=0.216,95%CI:0.093-0.505);T等位基因分布在病例组显著升高(61.3%vs 38.7%,P=0.006)。②129例研究对象中TT基因型血同型半胱氨酸水平显著升高(P=0.000):TT为19.0±9.5 nmol/L、CC为13.1±6.2 nmol/L、CT为11.7±4.0 nmol/L,病例组和对照组高Hcy水平组间无统计学差异(P>0.05)。③病例组中有38.0%(27/71)为高Hcy血症,叶酸治疗有效。结论:MTHFR基因多态性(C677T)与复发性流产有关;MTHFR基因TT型与高Hcy血症有关;叶酸可用于治疗高Hcy血症且有助于改善下次妊娠结局。

Objective： To investigate the association of the polymorphism of 5,10-methylenetetra hydrofolate reductase （MTHFR） C677T, and homocystine with recurrent pregnancy loss （RPL）. Methods： A case-control study was conducted on 71 cases of RPL patients （case group） and 58 healthy women （the control）. The polymor- phism of MTHFR C677T was genotyped by PCR-RFLP. The plasma level of homocysteine （Hcy） was tested by enzyme-linked immunosorbent assay （ELISA）. The next pregnancy outcome of case group was followed up. Results： 1） The distribution frequencies of C677T genotypes between case group and the control showed a statistically significant difference （P=0.00 I）. The frequencies of C677T genotypes were CC （14.1%）, CT （49.3%）, TT （36.6%） in case group and CC （43.1%）, CT （25.9%）, TT （31.0%） in the control. And the frequency of CC genotype in case group was decreased significantly （P=0.000, OR= 0.216, 95%Ch 0.093-0.505）, while the frequency of T allele in case group was increased （61.3% vs 38.7%, P=0.006）. 2） The plasma Hcy level was remarkable higher in women with TT genotypes than that in women with C/C genotypes （P=0.000）, TT： 19.0 ±9.5 nmol/L, CC： 13.1±6.2 nmol/L, CT： 11.7 ＋_ 4.0 nmol/L. The plasma Hcy level was not different between the case group and the control. 3） Twenty-seven women in case group got high homocysteine level （38.0%）. Folic acid was an effective treatment for them reducing their Hcy level. Conclusion： The polymorphism of MTHFR gene mutions C677T is related to RPL. Polymorphism of MTHFR gene mutions can cause high plasma Hcy level. Folic acid treatment is effective to control plasma Hcy level and can be useful to improve the next pregnancy outcome.