Association of a GATA Binding Protein 4 Polymorphism with the Risk of Hypospadias in the Chinese Children

Abstract

<b><i>Purpose:</i></b> GATA binding protein 4 (GATA4) has been implicated in the etiology of congenital malformation of the urogenital system. The present study investigated the influence of <i>GATA4</i> polymorphisms on susceptibility to hypospadias. <b><i>Methods:</i></b> We genotyped 4 potentially functional polymorphisms (rs12458, rs12825, rs884662, and rs904018) in <i>GATA4</i> in the hospital-based case-control study including 410 child patients and 520 nonmalformed individuals by the TaqMan MGB method. Risk associations were assessed using unconditional logistic regression, adjusted for potential confounding factors. <b><i>Results:</i></b> A significant association was found between rs12458 (3′-UTR of <i>GATA4</i>) and susceptibility to hypospadias (<i>p</i> = 0.008). Compared with rs12458 AA genotype individuals, those harboring the variant allele (rs12458 AT/TT) were correlated with significantly higher risk of hypospadias (AT/TT vs. AA: OR = 1.42, 95% CI = 1.17–2.35, <i>p</i> = 0.036). Furthermore, the rs12458T allele showed significantly decreased activity in a luciferase reporter assay, indicating a possible role of rs12458 variant in regulating the combination of microRNAs with the <i>GATA4</i> mRNA. <b><i>Conclusions:</i></b> The present results indicate that the functional <i>GATA4</i> rs12458 variant confers individuals’ susceptibility to hypospadias, possibly through regulating the <i>GATA4</i> expression level.