Genetic Variation in the Vascular Endothelial Growth Factor Gene is Associated With Biliary Atresia

Biliary atresia (BA) is a chronic inflammatory disease of the bile ducts resulting in biliary cirrhosis. Vascular endothelial growth factor (VEGF) has been implicated in cell-mediated inflammatory reactions. We aimed to study the relationship between genetic variations of the VEGF gene and susceptibility to BA using both case-control and family-based methodologies.A total of 45 Taiwanese children with BA, 160 ethnically matched healthy controls, and 40 families (consisting of parents, affected children, and unaffected siblings) were studied. Three functional VEGF polymorphisms (-2578 A/C, -634 G/C, and +936 C/T) were assessed by using TaqMan assay.The +936 CC genotype [odds ratio (OR) 3.51, 95% confidence interval 1.54-8.01, P(c)=0.006] and C allele (OR 3.19, 95% confidence interval 1.48-6.90, P(c)=0.004) were significantly associated with increased risk of BA. The association of the +936 C allele with BA was also confirmed in a family-based association study (OR 5.7, chi2=9.8, P(c)=0.005). None of the haplotypes studied significantly influenced the risk to BA in either the case-control or family data sets.The VEGF +936 C/T polymorphism and particularly the C allele are associated with BA, possibly conferring increased susceptibility to the disease.