Truncating Mutation in FOXC2 Gene in Familial Hemorrhoids and Varicose Veins

Abstract

Hemorrhoids and varicose veins are conditions resulting from loss of vascular integrity and, despite being worldwide health concerns, their pathogenesis has not been clearly defined. Many risk factors have been linked to the development of these complications including diet, defecating habits, alcohol consumption and other physiological factors. There are limited studies involving the possible role of genetic mutations in the development of hemorrhoids and varicose veins. FoxC2 is an important transcription factor that plays many roles in a variety of embryonic developmental processes, including angiogenesis. In the current study, we aimed to investigate the role of the FOXC2 gene variations in the development of familial hemorrhoids and varicose veins in the Jordanian population. Thirty-two samples were collected from eight families manifested hemorrhoids and/or varicose veins conditions. DNA sequencing was performed to screen variation in the FOXC2 gene. Two individuals with severe and early onset of hemorrhoids and varicose veins from the same family showed a frameshift mutation (881'inT) in the coding exon of the FOXC2 gene resulting in a premature stop codon at position +1386 (294 residues truncated peptide). In conclusion, our results support a possible role of genetic predisposition in the development of hemorrhoids and varicose veins with a frequency of 6% in the selected population