title: Haplotypes of heparin-binding epidermal-growth-factor-like growth factor gene are associated with pre-eclampsia.
abstract: OBJECTIVE
  Heparin-binding epidermal-growth-factor-like growth factor (HBEGF) plays an important role in placentation, including impaired placentation, the primary defect seen in pre-eclampsia. We carried out a case-control disease-association study to examine the association of single nucleotide polymorphisms (SNP) in the HBEGF gene and haplotypes defined by them with pre-eclampsia in a Sinhalese population in Sri Lanka.
  
  
  METHODS
  A total of 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for six SNP selected in silico as having putative functional effects using mass array Sequenom iplex methodology and a newly designed polymerase chain reaction-restriction fragment length polymorphism assay.
  
  
  RESULTS
  The individual SNP were not associated with pre-eclampsia. The haplotypes defined by them, however, showed both predisposing (rs13385T,rs2074613G,rs2237076G,rs2074611C,rs4150196A,rs1862176A; odds ratio,1.65; 95% confidence interval1.04-2.60; P=0.032) and protective (rs13385C,rs2074613G,rs2237076A,rs2074611C,rs4150196A,rs1862176A; odds ratio,0.20; 95% confidence interval, 0.04-0.89; P=0.034) effects.
  
  
  CONCLUSIONS
  These results confirm that polymorphisms in the HGEGF gene are associated with pre-eclampsia. The haplotypes are likely to exert their effects through the numerous transcription regulation factors binding to the polymorphic sites, namely GATA-1, GATA-3, MZF-1 and AML-1a.
authors.affiliation: Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka. gayanihg@gmail.com
authors.forename: Galhenagey Gayani
authors.initials: GG
authors.lastname: Harendra
authors.forename: Rohan W
authors.initials: RW
authors.lastname: Jayasekara
authors.forename: Vajira H W
authors.initials: VH
authors.lastname: Dissanayake
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy
chemical_list: C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins