亚甲基四氢叶酸还原酶（MTHFR）与胸苷酸合成酶增强子区域（TSER）基因多态性联合对韩国复发性自然流产患者血浆同型半胱氨酸水平的影响

Influence of combined methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase enhancer region (TSER) polymorphisms to plasma homocysteine levels in Korean patients with recurrent spontaneous abortion.

作者信息

Kim Nam Keun, Choi Yoon Kyung, Kang Myung Seo, Choi Dong Hee, Cha Sun Hee, An Myung Ok, Lee Suman, Jeung Mingull, Ko Jung Jae, Oh Doyeun

机构信息

Institute for Clinical Research, Bundang CHA General Hospital, College of Medicine, Pochon CHA University, 351, Yatap-dong, Bundang-gu, Seongnam, Kyunggi-do, 463-712, South Korea.

出版信息

Thromb Res. 2006;117(6):653-8. doi: 10.1016/j.thromres.2005.05.025. Epub 2005 Jun 27.

DOI:10.1016/j.thromres.2005.05.025

PMID:15985285

Abstract

OBJECTIVES

Methylenetetrahydrofolate reductase (MTHFR) mutations known to be associated with hyperhomocysteinemia may be a risk factor for recurrent spontaneous abortion. Recently 28-bp tandem repeat polymorphism in thymidylate synthase enhancer region (TSER) was reported to affect plasma homocysteine level. We investigated the association between plasma homocysteine level and MTHFR and TSER genotypes.

METHODS

Plasma homocysteine level was measured by fluorescent polarizing immunoassay. MTHFR mutations (C677T and A1298C) were identified by PCR-restriction fragment length polymorphism assay. TSER mutation was analyzed by PCR method.

RESULTS

Average homocysteine level was significantly higher in MTHFR 677TT genotype (9.80+/-3.87 micromol/L) than in MTHFR 677CT (7.04+/-1.99 micromol/L) in MTHFR 677CC genotype (8.14+/-1.74 micromol/L) in Korean patients with unexplained recurrent spontaneous abortion (p=0.0143). While MTHFR 1298AA showed the highest level, plasma homocysteine levels were not significantly different among MTHFR 1298AA (8.42+/-2.65 micromol/L), 1298AC (6.98+/-2.44 micromol/L) and 1298CC (6.09+/-0.32 micromol/L) (p=0.2058). There was no significant difference among TSER genotypes (2R2R, 8.61+/-1.68 micromol/L; 2R3R, 7.84+/-2.16 micromol/L; 3R3R, 8.05+/-2.81 micromol/L; p=0.9319). Among the combined genotypes of MTHFR C677T and TSER, 677TT-3R3R genotype had the highest homocysteine level (11.47+/-4.66 micromol/L). 1298AA-3R3R had the highest level (8.54+/-3.05 micromol/L) among the combined genotypes of MTHFR A1298C and TSER.

CONCLUSION

Although there was no significant difference found among combined genotypes, 3R3R showed elevated homocysteine levels in MTHFR 677TT and 1298AA in Korean patients with unexplained recurrent spontaneous abortion. Thus TSER polymorphism may be a genetic determinant of plasma homocysteine level in Korean patients as well as MTHFR C677T polymorphism.

摘要

目的

已知亚甲基四氢叶酸还原酶（MTHFR）突变与高同型半胱氨酸血症相关，可能是复发性自然流产的一个危险因素。最近有报道称胸苷酸合成酶增强子区域（TSER）的28 bp串联重复多态性会影响血浆同型半胱氨酸水平。我们研究了血浆同型半胱氨酸水平与MTHFR及TSER基因型之间的关联。

方法

采用荧光偏振免疫分析法测定血浆同型半胱氨酸水平。通过聚合酶链反应-限制性片段长度多态性分析法鉴定MTHFR突变（C677T和A1298C）。采用聚合酶链反应法分析TSER突变。

结果

在原因不明的复发性自然流产韩国患者中，MTHFR 677TT基因型（9.80±3.87 μmol/L）的平均同型半胱氨酸水平显著高于MTHFR 677CT基因型（7.04±1.99 μmol/L）和MTHFR 677CC基因型（8.14±1.74 μmol/L）（p = 0.0143）。虽然MTHFR 1298AA显示出最高水平，但MTHFR 1298AA（8.42±2.65 μmol/L）、1298AC（6.98±2.44 μmol/L）和1298CC（6.09±0.32 μmol/L）之间的血浆同型半胱氨酸水平无显著差异（p = 0.2058）。TSER基因型之间无显著差异（2R2R，8.61±1.68 μmol/L；2R3R，7.84±2.16 μmol/L；3R3R，8.05±2.81 μmol/L；p = 0.9319）。在MTHFR C677T和TSER的联合基因型中，677TT - 3R3R基因型的同型半胱氨酸水平最高（11.47±4.66 μmol/L）。在MTHFR A1298C和TSER的联合基因型中，1298AA - 3R3R的水平最高（8.54±3.05 μmol/L）。