• PMID: 21113153
• Gene Name: DGKK
• Condition: Hypospadias
• Association: Associated
• Mutation: rs1934179 and rs7063116
• Population size: 1731
• Population details: 1731 (436 individuals with hypospadias (cases), 494 controls, 133 cases and their parents, and a Swedish series of 266 cases and 402 controls)
• Sex: Male
• Infertility type: Male infertility

Common variants in DGKK are strongly associated with risk of hypospadias

van der Zanden LF, van Rooij IA, Feitz WF, Knight J, Donders AR, Renkema KY, Bongers EM, Vermeulen SH, Kiemeney LA, Veltman JA, Arias-V�squez A, Zhang X, Markljung E, Qiao L, Baskin LS, Nordenskj�ld A, Roeleveld N, Franke B, Knoers NV.

Hypospadias is a common congenital malformation of the male external genitalia. We performed a genome-wide association study using pooled DNA from 436 individuals with hypospadias (cases) and 494 controls of European descent and selected the highest ranked SNPs for individual genotyping in the discovery sample, an additional Dutch sample of 133 cases and their parents, and a Swedish series of 266 cases and 402 controls. Individual genotyping of two SNPs (rs1934179 and rs7063116) in DGKK, encoding diacylglycerol kinase κ, produced compelling evidence for association with hypospadias in the discovery sample (allele-specific odds ratio (OR) = 2.5, P = 2.5 × 10⁻¹¹ and OR = 2.3, P = 2.9 × 10⁻⁹, respectively) and in the Dutch (OR = 3.9, P = 2.4 × 10⁻⁵ and OR = 3.8, P = 3.4 × 10⁻⁵) and Swedish (OR = 2.5, P = 2.6 × 10⁻⁸ and OR = 2.2, P = 2.7 × 10⁻⁶) replication samples. Expression studies showed expression of DGKK in preputial tissue of cases and controls, which was lower in carriers of the risk allele of rs1934179 (P = 0.047). We propose DGKK as a major risk gene for hypospadias. FAU - van der Zanden, Loes F M AU - van der Zanden LF AD - Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. FAU - van Rooij, Iris A L M AU - van Rooij IA FAU - Feitz, Wout F J AU - Feitz WF FAU - Knight, Jo AU - Knight J FAU - Donders, A Rogier T AU - Donders AR FAU - Renkema, Kirsten Y AU - Renkema KY FAU - Bongers, Ernie M H F AU - Bongers EM FAU - Vermeulen, Sita H H M AU - Vermeulen SH FAU - Kiemeney, Lambertus A L M AU - Kiemeney LA FAU - Veltman, Joris A AU - Veltman JA FAU - Arias-Vásquez, Alejandro AU - Arias-Vásquez A FAU - Zhang, Xufeng AU - Zhang X FAU - Markljung, Ellen AU - Markljung E FAU - Qiao, Liang AU - Qiao L FAU - Baskin, Laurence S AU - Baskin LS FAU - Nordenskjöld, Agneta AU - Nordenskjöld A FAU - Roeleveld, Nel AU - Roeleveld N FAU - Franke, Barbara AU - Franke B