GATA4基因遗传变异与中国人群先天性尿道下裂发病机制的研究

Hypospadias is one of the most common congenital defects in genitourinary system. GATA4 plays a crucial role in the process of genital development through mediating the expression of sex determining region and SOX9 genes. It has been reported that loss of function mutation in GATA4 caused anomalies of human testicular development. In this study, we will investigate the influence of genetic variation in GATA4on the development of hypospadias. The preliminary studies have found that an rs12825 C>G variation in the 3’UTR region of GATA4was significantly associated with increased risk of hypospadias. Besides, the mRNA level of GATA4 was apparently reduced in the urethral tissue. The project intends to further investigate the mechanism underlying the regulation of rs12825 C>G variation on the .expression of GATA4. The results of the project may contribute to the efforts directed to a better understanding of the development of hypospadias.

先天性尿道下裂是男性泌尿生殖系统最常见的先天性发育异常之一。GATA4通过调控Y染色体上的性别决定区（SRY）以及SOX9等基因在生殖发.育过程中起到重要作用。已有研究发现GATA4基因突变导致人类睾丸发育异常。本课题拟探讨GATA4基因遗传变异在先天性尿道下裂发生中的作用以及可能的生物学机制。前期研究发现位于GATA43’UTR区域的rs12825 C>G位点和先天性尿道下裂的发病风险明显相关。且携带rs12825 CG/GG 基因型的尿道组织中GATA4基因mRNA表达水平明显降低。本课题拟采用多种生物学技术和方法进一步研究该突变对GATA4基因转录后调控的影响及其可能的分子机制。初步阐明GATA4参与先天性尿道下裂发生的可能生物学机制。