PDGFA gene rs9690350 polymorphism increases biliary atresia risk in Chinese children

Abstract

Biliary atresia (BA) is a genetic and severe fibro-inflammatory obliterative cholangiopathy of neonates. Platelet-derived growth factor subunit A (PDGFA), as one of participants in liver fibrosis, the overexpression of PDGFA through DNA hypomethylation may lead to the development of BA, but the pathogenesis is still unclear. We conducted a large case-control cohort to investigate the association of genetic variants in PDGFA with BA susceptibility in the Southern Chinese population (506 cases and 1473 controls). We observed that the G allele of rs9690350(G>C) in PDGFA was significantly associated with an increased risk of BA (OR=1.24, 95% CI=1.04-1.49, P=0.02). Additionally, the rs9690350 G allele increased the risk of non-cystic biliary atresia (OR=1.26, 95% CI=1.04-1.52, P=0.02) and was a genetic biomarker of severe manifestations after surgery. These findings indicate that the rs9690350 G allele is a PDGFA polymorphism associated with the risk of BA that may confer increased disease susceptibility.

Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy

“…PDGFA, which has one SNP association 65 , and significant hypomethylation in some BA patients 66 , is also of interest and heavily expressed in the hepatic endothelium 117 . The discovery of SNPs in these inter-related genes highlights the neo-angiogenic cross-talk within the biliary epithelium and nearby endothelial cells in events of cellular stress.…”

Genetic Factors and Their Role in the Pathogenesis of Biliary Atresia

“…In 2020, Liu et al demonstrated that the G allele in rs9690350 of PDGFA (platelet-derived growth factor subunit) markedly increased the susceptibility for BA in newborns (32). PDGFA is located in 7p22 and encodes PDGFA.…”

“…Since 1995 it has been known that inflammation and fibrosis are correlated with TGF-β1 and PDGF levels in liver BA ( 76 ). In 2020, Liu et al demonstrated that the G allele in rs9690350 of PDGFA (platelet-derived growth factor subunit) markedly increased the susceptibility for BA in newborns ( 32 ). PDGFA is located in 7p22 and encodes PDGFA.…”

Geneticheskiye aspekty etiologii biliarnoy atrezii

“…Белки семейства PDGF индуцируют пролиферативные и фиброзные патологии во многих органах. Так, вариант rs9690350 (G>C) в PDGFA был связан с повышенным риском БА в группе 506 пациентов с БА против 1473 здоровых [99].…”