maintext

Further Evidence of the Association of the Diacylglycerol Kinase Kappa (DGKK) Gene With Hypospadias

Kamil Konrad Hozyasz, Adrianna Mostowska, Andrzej Kowal, Dariusz Mydlak, Alexander Tsibulski, Pawe? P. Jagodzi?ski

Abstract


375

Purpose: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: Our study provides strong evidence of an association between DGKK nucleotide variants, haplotypes and hypospadias susceptibility.

Full Text:

PDF

44

References


George M, Schneuer FJ, Jamieson SE, Holland AJ. Genetic and environmental factors in the aetiology of hypospadias. Pediatr Surg Int. 2015; 31: 519-27.

Gite VA, Nikose JV, Bote SM, Patil SR. Anterior urethral advancement as a singlestage technique for repair of anterior

hypospadias: our experience. Urol J. 2017;14:4034-37.

Kalfa N, Paris F, Philibert P, et al. Is hypospadias associated with prenatal exposure to endocrine disruptors? A French collaborative controlled study of a cohort of 300 consecutive children without genetic defect. Eur Urol. 2015; 68:1023-30.

Choudhry S, Baskin LS, Lammer EJ, et al. Genetic polymorphisms in ESR1 and ESR2 genes and risk of hypospadias in a multiethnic study population. J Urol. 2015;193:1625-31.

van der Zanden LF, van Rooij IA, Feitz WF, et al. Common variants in DGKK are strongly associated with risk of hypospadias. Nat Genet. 2011;43: 48-50.

Geller F, Feenstra B, Carstensen L, et al. Genome-wide association analyses identify variants in developmental genes associated with hypospadias. Nat Genet. 2014;46:957-63.

Carmichael SL, Mohammed N, Ma C, et al. Diacylglycerol kinase k variants impact hypospadias in a California study population.

J Urol. 2013;189: 305-11.

Ma Q, Tang Y, Lin H, et al. Diacylglycerol kinase k (DGKK) variants and hypospadias in Han Chineses: association and meta-analysis. BJU Int. 2015;116: 634-640.

Shionoya T, Usuki T, Komenoi S, Isozaki T, Sakai H, Sakane F. Distinct expression and localization of the type II diacylglycerol

kinase isozymes δ, η and κ in the mouse reproductive organs. BMC Dev Biol. 2015;15:6.

Wu C, Li S, Cui Y. Genetic association studies: an information content perspective. Curr Genom. 2012;13: 566-73.

Palmsten K, Chambers CD. Hypospadias: one defect, multiple causes, acting through shared pathways. Curr Epidemiol Rep. 2015; 2: 13-22.

Polat H, Gulacti U. The ideal use of catheters in hypospadias repair: An experimental study. Urol J. 2016; 13: 2856-9.

Shen J, Liu B, Sinclair A, Cunha G, Baskin LS, Choudhry S. Expression analysis of DGKK during external genitalia formation. J

Urol. 2015; 194:1728-36.

Snodgrass WT, Bush NC. Hypospadias. In: Snodgrass WT, editor. Pediatric Urology. Evidence for Optimal Patient Management. New York: Springer; 2013. p.117-52.

Liu N, Zhang K, Zhao H. Haplotypeassociation analysis. Adv Genet. 2008; 60: 335-405.

Clark AG. The role of haplotypes in candidate gene studies. Genet Epidemiol. 2004; 27: 321-33.

Xie H, Lin X-L, Zhang S, et al. Asssociation between diacylglycerol kinase kappa variants and hypospadias susceptibility in a Han Chinese population. Asian J Androl. 2017;

doi: 10.4103/aja.aja_13_17.




DOI: http://dx.doi.org/10.22037/uj.v0i0.4061


Creative Commons License 
This work is licensed under a Creative Commons Attribution 3.0 License