The association of single nucleotide polymorphisms of the maternal cystathionine-β-synthase gene with early-onset preeclampsia
The association of single nucleotide polymorphisms of the maternal cystathionine-β-synthase gene with early-onset preeclampsia
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DOI：
10.1016/j.preghy.2015.12.001
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发表时间：
2016-01-01
影响因子：
2.2
通讯作者：
Faas, Marijke M.
中科院分区：
文献类型：
--
作者：
Holwerda, Kim M.;Weedon-Fekjaer, M. Susanne;Faas, Marijke M.
目的：子痫前期（Preeclampsia，PE）是一种以高血压和蛋白尿为特征的妊娠并发症.转硫途径可能参与其病理生理学，因为同型半胱氨酸，胱硫醚和半胱氨酸在PE中增加。胱硫醚-β-合酶（CBS）是该途径中的关键酶，通过胱硫醚将同型半胱氨酸转化为半胱氨酸。CBS的另一种产物是硫化氢（H2S），这是一种血管扩张、促血管生成和细胞保护气体，被认为在妊娠期间对胎盘和血管功能起作用。由于单核苷酸多态性（single nucleotide polymorphism，SNPs）可影响CBS基因的表达和/或功能，我们研究了PE患者CBS基因中的tag-SNPs。rs 12329764、rs 2851391、rs 234713、rs 234706、rs 1789953和rs 11203172。妊娠期间测定血浆同型半胱氨酸、半胱氨酸和胱硫醚。主要观察指标：早发性肺栓塞，晚发性肺栓塞。结果：携带rs 11203172次要等位基因的女性早发性肺栓塞的风险降低。与没有次要等位基因的女性相比，具有次要等位基因rs 11203172和rs 234713的血压正常的孕妇具有较低的半胱氨酸水平。与不具有次要等位基因rs 1789953的女性相比，具有次要等位基因rs 1789953的女性半胱氨酸和胱硫醚水平升高。结论：CBS tag-SNP rs 11203172与早发性PE的风险降低相关。携带rs 11203172次要等位基因的血压正常孕妇的半胱氨酸浓度降低，可能是由于CBS增加了半胱氨酸转化为H2S。较高的H2S水平可能对妊娠期间的胎盘形成和血管功能产生积极影响，并降低PE的风险。(C)2015年国际妊娠高血压研究学会。Elsevier B. V.出版，保留所有权利。
Objectives: Preeclampsia (PE) is a pregnancy complication, characterized by hypertension and proteinuria. The transsulfuration pathway may be involved in its pathophysiology, since homocysteine, cystathionine and cysteine are increased in PE. Cystathionine-beta-synthase (CBS) is a key-enzyme in the pathway, converting homocysteine into cysteine via cystathionine. Another product of CBS is hydrogen sulfide (H2S), a vasodilatory, proangiogenic and cytoprotective gas that is thought to play a role in placental and vascular function during pregnancy. Since single nucleotide polymorphisms (SNPs) can affect CBS expression and/or function, we studied tag-SNPs in the CBS gene in PE patients.Study design: Controls (n = 75), early-onset (n = 45), and late-onset PE (n = 52) cases were genotyped for six tag-SNPs in the CBS gene; rs12329764, rs2851391, rs234713, rs234706, rs1789953, and rs11203172. Plasma homocysteine, cysteine and cystathionine were determined during pregnancy. Main outcome measures: Early-onset PE, late-onset PE.Results: Women with the minor allele of rs11203172 have a reduced risk for early-onset PE. Compared to women without the minor allele, normotensive pregnant women with the minor allele of rs11203172 and rs234713 have lower cysteine levels. Women with the minor allele of rs1789953 have increased levels of cysteine and cystathionine, compared to women without.Conclusion: The CBS tag-SNP rs11203172 is associated with a decreased risk for early-onset PE. Decreased cysteine concentrations in normotensive pregnant women carrying the minor allele of rs11203172, may be due to increased cysteine conversion to H2S by CBS. Higher H2S levels may positively affect placentation and vascular" function during pregnancy and decrease their risk for PE. (C) 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.