title: Polymorphism in the epidermal growth factor gene is associated with pre-eclampsia and low birthweight.
abstract: OBJECTIVE
  We have previously reported that polymorphism in the epidermal growth factor (EGF) gene is associated with pre-eclampsia and birthweight based on case-control association studies involving two single nucleotide polymorphisms (SNP). We extended that work to investigate other SNP in the EGF gene for their association with pre-eclampsia and the weight of babies at birth.
  
  
  METHODS
  A population-based DNA collection was genotyped to determine whether the selected SNP were polymorphic in the study population. In total, 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for the polymorphic SNP using polymerase chain reaction/restriction fragment length polymorphism and MassARRAY Sequenom iPLEX methodology.
  
  
  RESULTS
  The rs3756261A, rs4444903G, rs2237051G haplotype was associated with the highest increased risk of pre-eclampsia (odds ratio: 3.70, 95% confidence interval: 1.38-9.94; P = 0.016). The rs3756261A allele was the one that contributed to this high degree of significance. The same allele was present in the haplotype rs3756261A, rs11568943G, rs2237051G, rs11569017A, rs4698803T (likelihood ratio statistic = 20.4671, d.f. = 3, P-value = 0.0001), which was associated with the lower birthweight.
  
  
  CONCLUSIONS
  In this study we found further evidence for the association of polymorphism in the EGF gene with pre-eclampsia and the weight of babies at birth and identified rs3756261A>G as the SNP that makes the most significant contribution to this association. Bioinformatic analysis showed that this effect may be mediated by caudal type homeohox-2, a transcriptional repressor expressed in the trophoblast, for which a binding site is created at this polymorphic site when the rs3756261A allele is present.
authors.affiliation: Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
authors.forename: Thurayratnam
authors.initials: T
authors.lastname: Chenthuran
authors.forename: Gayani Harendra
authors.initials: GH
authors.lastname: Galhenagey
authors.forename: Rohan W
authors.initials: RW
authors.lastname: Jayasekara
authors.forename: Vajira H W
authors.initials: VH
authors.lastname: Dissanayake
mesh_terms: D000293:Adolescent; D000328:Adult; D000071616:CDX2 Transcription Factor; D016022:Case-Control Studies; D004815:Epidermal Growth Factor / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D040641:Quantitative Trait Loci
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D004815:Epidermal Growth Factor
keywords: birthweight; case-control studies; epidermal growth factor; haplotypes; pre-eclampsia