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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).    Conclusion  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.

Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa)