Raijmakers M T, Zusterzeel P L, Steegers E A, Peters W H
Department of Gastroenterology, University Hospital St. Radboud, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Eur J Obstet Gynecol Reprod Biol. 2001 Apr;95(2):226-8. doi: 10.1016/s0301-2115(00)00497-8.
Preeclampsia represents one of the most frequent complications of pregnancy, however, little is known about its aetiology. Damage of the endothelial layer lining the blood vessel wall is thought to play an important role in the pathophysiology of preeclampsia, accordingly, mild hyperhomocysteinaemia has been reported to be more prevalent among preeclamptic women. Therefore, we investigated the role of hyperhomocysteinaemia in preeclampsia by measuring plasma levels of homocysteine and studying the prevalence of the 677(C-->T) polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, which may lead to reduced MTHFR enzyme activity and subsequently to higher plasma homocysteine levels. Plasma samples of 10 healthy non-pregnant women, 10 normotensive pregnant women, and 20 women with preeclampsia were analysed for total homocysteine levels by high performance liquid chromatography. Furthermore, 167 Dutch non-pregnant women previously hospitalised for preeclampsia and 403 population-based controls were analysed for the 677(C-->T) polymorphism by polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR/RFLP). In normotensive pregnancy homocysteine levels were lower compared with levels in healthy non-pregnant controls (8.4 versus 13.7micromol/l, P<0.001). Women with preeclampsia showed higher concentrations than women during normotensive pregnancy (13.3 versus 8.4micromol/l, P<0.02). However, levels of homocysteine in preeclampsia were comparable to those found in healthy non-pregnant women. PCR/RFLP showed no significant difference in the incidence of the 677(C-->T) polymorphism in the MTHFR gene between preeclamptic women with or without HELLP syndrome and controls (13 and 9% homozygous for the less common T-allele, respectively; OR 1.5, 95% CI 0.8-2.6, P=0.17). In contrast with previous reports, we cannot confirm that mild hyperhomocysteinaemia is a risk factor for preeclampsia. Pregnancy induced hyperhomocysteinaemia found in preeclampsia might better be explained by fluctuations in plasma volume than by the presence of the 677(C-->T) polymorphism in the MTHFR gene.
子痫前期是妊娠最常见的并发症之一，然而，其病因却鲜为人知。血管壁内衬的内皮细胞层受损被认为在子痫前期的病理生理学中起重要作用，因此，据报道轻度高同型半胱氨酸血症在子痫前期女性中更为普遍。因此，我们通过测量血浆同型半胱氨酸水平以及研究5,10-亚甲基四氢叶酸还原酶（MTHFR）基因中677（C→T）多态性的患病率，来探讨高同型半胱氨酸血症在子痫前期中的作用，该多态性可能导致MTHFR酶活性降低，进而导致血浆同型半胱氨酸水平升高。采用高效液相色谱法分析了10名健康非妊娠女性、10名血压正常的妊娠女性和20名单纯性高血压女性的血浆样本中的总同型半胱氨酸水平。此外，对167名曾因子痫前期住院的荷兰非妊娠女性和403名基于人群的对照者，采用聚合酶链反应（PCR）及随后的限制性片段长度多态性分析（PCR/RFLP），分析其677（C→T）多态性。与健康非妊娠对照组相比，血压正常的妊娠女性同型半胱氨酸水平较低（8.4对13.7μmol/L，P<0.001）。子痫前期女性的同型半胱氨酸浓度高于血压正常的妊娠女性（13.3对8.4μmol/L，P<0.02）。然而，子痫前期患者的同型半胱氨酸水平与健康非妊娠女性相当。PCR/RFLP显示，无论有无HELLP综合征，子痫前期女性与对照组MTHFR基因677（C→T）多态性的发生率无显著差异（分别有13%和9%的患者为罕见T等位基因纯合子；比值比1.5，95%可信区间0.8-2.6，P=0.17）。与之前的报道相反，我们无法证实轻度高同型半胱氨酸血症是子痫前期的危险因素。子痫前期中发现的妊娠诱导性高同型半胱氨酸血症，可能更好地用血浆容量波动来解释，而非MTHFR基因中677（C→T）多态性的存在。
