Association of common genetic variants in VEGFA with biliary atresia susceptibility in Northwestern Han Chinese

Abstract

Biliary atresia (BA) is a major neonatal obliterative cholangiopathy, resulting in progressive cirrhosis. The gene VEGFA encodes a heparin-binding protein that is a regulator of angiogenesis and a mediator of inflammatory reactions, and accumulating evidence have indicated that VEGFA may play a possible role in the pathogenesis of BA. Our study aim was to evaluate the association of common variants within the VEGFA gene with BA susceptibility in Northwestern Han Chinese population. Forty tag SNPs within the VEGFA gene were selected in the study, and then subsequently genotyped in 1336 Northwestern Han Chinese individuals, consisting of 311 BA patients and 1025 healthy controls. The SNP rs3025039 was found to be strongly associated with BA risk (additive P=0.000264) in our sample, and the CC genotype of rs3025039 had higher prevalence than the other two genotypes, indicating the C allele is a risk allele with an odds ratio (OR) of 1.56 and 95% confidence interval (CI) of 1.23–1.99. Haplotype analyses showed that a LD block containing rs3025039 significantly correlated with BA risk (global P<0.001). Moreover, bioinformatics analysis indicated that hsa-mir-591 and VEGFA formed miRNA/SNP target duplexes if the rs3025039 allele was in the T form, suggesting that rs3025039 may alter VEGFA expression by affecting hsa-miR-591/single-nucleotide polymorphism target duplexes. Our results indicate additional evidence supporting that there is an important role of the VEGFA gene in the increased susceptibility of BA. AbbreviationsImage 1BABiliary atresiaGWASgenome-wide association studiesSNPsingle-nucleotide polymorphismMAFminor allele frequenciesHWEHardy-Weinberg equilibriumORsOdds ratiosCIsconfidence intervalsLDlinkage disequilibriumUTRuntranslated region