title: The association of single nucleotide polymorphisms of the maternal cystathionine-β-synthase gene with early-onset preeclampsia.
abstract: OBJECTIVE
  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-β-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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30001, 9713 GZ Groningen, The Netherlands. Electronic address: k.m.holwerda@umcg.nl.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Holwerda
authors.affiliation: University of Oslo, Department of Obstetrics and Gynaecology, Oslo University Hospital, Ulleval, 0424 Oslo, Norway. Electronic address: m.s.weedon-fekjar@biotek.uio.no.
authors.forename: M Susanne
authors.initials: MS
authors.lastname: Weedon-Fekjær
authors.affiliation: University of Oslo, Department of Obstetrics and Gynaecology, Oslo University Hospital, Ulleval, 0424 Oslo, Norway. Electronic address: UXNNAF@ous-hf.no.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Staff
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30001, 9713 GZ Groningen, The Netherlands. Electronic address: i.m.nolte@umcg.nl.
authors.forename: Ilja M
authors.initials: IM
authors.lastname: Nolte
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30001, 9713 GZ Groningen, The Netherlands. Electronic address: h.van.goor@umcg.nl.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: A.T.Lely@umcutrecht.nl.
authors.forename: A Titia
authors.initials: AT
authors.lastname: Lely
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30001, 9713 GZ Groningen, The Netherlands; Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: m.m.faas@umcg.nl.
authors.forename: Marijke M
authors.initials: MM
authors.lastname: Faas
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D003540:Cystathionine / Q000097:blood; D003541:Cystathionine beta-Synthase / Q000235:genetics* / Q000378:metabolism; D003545:Cysteine / Q000097:blood; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006710:Homocysteine / Q000097:blood; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D011247:Pregnancy; D065840:Protective Factors; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D003540:Cystathionine; D003541:Cystathionine beta-Synthase; D003545:Cysteine
keywords: Cystathionine-β-synthase; Hydrogen sulfide; Preeclampsia; Single nucleotide polymorphisms; Transsulfuration pathway