title: Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa).
abstract: BACKGROUND
  Vascular endothelial growth factor A (VEGFA) is a major regulator of both physiological and pathological angiogenesis. Associations between polymorphisms in VEGFA and complex disease have been inconsistent. The parent from whom the allele was inherited may account for these inconsistencies. This study examined the parent of origin effect on the expression of murine Vegfa.
  
  
  METHODS
  Two homozygous, inbred mouse strains A/J (AJ) and 129x1/SvJ (129) were crossed to produce reciprocal AJ129 and 129AJ offspring, respectively. RNA was extracted from cardiac tissue of 6 week old male (n = 8) and female (n = 8) parental, and male and female F1 offspring mice (AJ129 n = 8 and 129AJ n = 8). Vegfa and Hif1a expression levels were measured by qPCR and compared between the F1 offspring from the reciprocal crosses.
  
  
  RESULTS
  We found significant differences in the expression of Vegfa in F1 offspring (AJ129 and 129AJ mice) of the reciprocal crosses between AJ and 129 mice. Offspring of male AJ mice had significantly higher expression of Vegfa than offspring of male 129 mice (p = 0.006). This difference in expression was not the result of preferential allele expression (allelic imbalance). Expression of Hif1a, a transcriptional regulator of Vegfa expression, was also higher in F1 offspring of an AJ father (p = 0.004).
  
  
  CONCLUSIONS
  Differences in Vegfa and Hif1a gene expression are likely the result of an upstream angiogenic regulator gene that is influenced by the parent of origin. These results highlight the importance of including inheritance information, such as parent of origin, when undertaking allelic association studies.
authors.affiliation: University of Western Sydney, School of Medicine, Penrith, NSW 2751, Locked Bag 1797, Australia. c.chiu@uws.edu.au
authors.forename: Christine L
authors.initials: CL
authors.lastname: Chiu
authors.forename: Chloe T
authors.initials: CT
authors.lastname: Morgan
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Lupton
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lind
mesh_terms: D022981:Allelic Imbalance; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D006720:Homozygote; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
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