Liu Bailing, Wei Jingli, Li Miao, Jiang Jue, Zhang Hui, Yang Li, Wu Haibin, Zhou Qi
Department of Ultrasound, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, China; Department of Ultrasound, Children's Hospital of Xi'an, Xi'an 710010, China.
Department of Ultrasound, Children's Hospital of Xi'an, Xi'an 710010, China.
Gene. 2017 Sep 10;628:87-92. doi: 10.1016/j.gene.2017.07.027. Epub 2017 Jul 12.
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.
胆道闭锁（BA）是一种主要的新生儿闭塞性胆管病，可导致进行性肝硬化。血管内皮生长因子A（VEGFA）基因编码一种肝素结合蛋白，该蛋白是血管生成的调节剂和炎症反应的介质，越来越多的证据表明VEGFA可能在BA的发病机制中发挥作用。我们的研究目的是评估VEGFA基因内常见变异与中国西北汉族人群BA易感性的关联。本研究选择了VEGFA基因内的40个标签单核苷酸多态性（tag SNPs），随后对1336名中国西北汉族个体进行基因分型，其中包括311例BA患者和1025名健康对照。在我们的样本中，发现单核苷酸多态性rs3025039与BA风险密切相关（加性模型P=0.000264），rs3025039的CC基因型患病率高于其他两种基因型，表明C等位基因是一个风险等位基因，优势比（OR）为1.56，95%置信区间（CI）为1.23 - 1.99。单倍型分析表明，包含rs3025039的连锁不平衡（LD）块与BA风险显著相关（整体P<0.001）。此外，生物信息学分析表明，如果rs3025039等位基因为T形式，hsa - mir - 591和VEGFA会形成miRNA/单核苷酸多态性靶标双链体，提示rs3025039可能通过影响hsa - miR - 591/单核苷酸多态性靶标双链体来改变VEGFA的表达。我们的结果提供了更多证据支持VEGFA基因在BA易感性增加中起重要作用。
