Hozyasz Kamil Konrad, Mostowska Adrianna, Kowal Andrzej, Mydlak Dariusz, Tsibulski Alexander, Jagodzinski Pawel P
Department of Paediatrics, Institute of Mother and Child, Warsaw, Poland.
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland.
Urol J. 2018 Sep 26;15(5):272-276. doi: 10.22037/uj.v0i0.4061.
Hypospadias is a common developmental anomaly of the male external genitalia. In previous studies conducted on West European, Californian, and Han Chinese populations the relationship between polymorphic variants of the diacylglycerol kinase kappa (DGKK) gene and hypospadias have been reported. The aim was to study the possible associations between polymorphic variants of the DGKK gene and hypospadias using an independent sample of the Polish population.
Ten single nucleotide polymorphisms in DGKK, which were reported to have an impact on the risk of hypospadias in other populations, were genotyped using high-resolution melting curve analysis in a group of 166 boys with isolated anterior (66%) and middle (34%) forms of hypospadias and 285 properly matched controls without congenital anomalies.
Two DGKK variants rs11091748 and rs12171755 were associated with increased risk of hypospadias in the Polish population. These results were statistically significant, even after applying the Bonferroni correction for multiple comparisons (P < .005). All the tested nucleotide variants were involved in haplotype combinations associated with hypospadias. The global p-values for haplotypes comprising of rs4143304-rs11091748, rs11091748-rs17328236, rs1934179-rs4554617, rs1934183-rs1934179-rs4554617 and rs12171755-rs1934183-rs1934179-rs4554617 were statistically significant, even after the permutation test correction.
Our study provides strong evidence of an association between DGKK nucleotide variants, haplotypes and hypospadias susceptibility.
尿道下裂是男性外生殖器常见的发育异常。在之前针对西欧、加利福尼亚和中国汉族人群开展的研究中，已报道了二酰甘油激酶κ（DGKK）基因多态性变异与尿道下裂之间的关系。本研究旨在利用波兰人群的独立样本，探讨DGKK基因多态性变异与尿道下裂之间可能存在的关联。
对166例患有孤立性前部（66%）和中部（34%）尿道下裂的男孩以及285例无先天性异常的匹配良好的对照进行高分辨率熔解曲线分析，对DGKK基因中据报道会影响其他人群尿道下裂风险的10个单核苷酸多态性进行基因分型。
两个DGKK变异体rs11091748和rs12171755与波兰人群尿道下裂风险增加相关。即使在应用Bonferroni多重比较校正后，这些结果仍具有统计学意义（P <.005）。所有检测的核苷酸变异均参与了与尿道下裂相关的单倍型组合。由rs4143304 - rs11091748、rs11091748 - rs17328236、rs1934179 - rs4554617、rs1934183 - rs1934179 - rs4554617以及rs12171755 - rs1934183 - rs1934179 - rs4554617组成的单倍型的总体P值即使在进行置换检验校正后仍具有统计学意义。
我们的研究为DGKK核苷酸变异、单倍型与尿道下裂易感性之间的关联提供了有力证据。
