Ma Qichao, Tang Yunman, Lin Houwei, Xu Maosheng, Xu Guofeng, Fang Xiaoliang, Chen Jianhua, Song Zhijian, Li Zhiqiang, Shi Yongyong, Geng Hongquan
Department of Pediatric Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pediatric Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
BJU Int. 2015 Oct;116(4):634-40. doi: 10.1111/bju.12965. Epub 2015 May 24.
To investigate whether diacylglycerol kinase κ (DGKK) is a susceptibility gene for hypospadias in the Han Chinese population as has been suggested by previous publications.
A case-control study involving 466 patients with hypospadias and 402 healthy subjects was conducted to assess the relationship between DGKK single nucleotide polymorphisms (SNPs) and hypospadias risk in the Han Chinese population. The 466 hypospadias patients were further divided into mild, moderate and severe subgroups for analysis.
Six SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs4826632 and rs4599945) were marginally associated with mild and moderate hypospadias [odds ratios (ORs) > 1, P = 0.05 to P < 0.1), whereas no significant relationship was seen with the severe cases (ORs >1, P > 0.1). After correcting for multiple testing, it was determined that neither individual SNPs nor individual haplotypes were associated with hypospadias. To evaluate this relationship in multiple populations, we performed a meta-analysis on six SNPs, using combined data from our present results and those of previous studies of different races (including 1966 patients and 2492 controls). Six SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs7063116 and rs1934190) were significantly associated with mild/moderate hypospadias (ORs >1, P < 0.05), and rs1934179 was significantly associated with severe hypospadias (OR > 1, P < 0.05).
DGKK gene variants do not appear to play a major role in hypospadias susceptibility in the Chinese Han population. Our meta-analysis supports the hypothesis that DGKK is a common risk gene for hypospadias, particularly in cases of mild or moderate hypospadias in Caucasian populations.
如先前出版物所提示，研究二酰基甘油激酶κ（DGKK）是否为中国汉族人群尿道下裂的易感基因。
患者、受试者与方法：开展一项病例对照研究，纳入466例尿道下裂患者和402例健康受试者，以评估DGKK单核苷酸多态性（SNP）与中国汉族人群尿道下裂风险之间的关系。将466例尿道下裂患者进一步分为轻度、中度和重度亚组进行分析。
六个SNP（rs1934179、rs4143304、rs9969978、rs1934188、rs4826632和rs4599945）与轻度和中度尿道下裂存在边缘关联[比值比（OR）>1，P = 0.05至P < 0.1]，而与重度病例无显著关联（OR>1，P>0.1）。在进行多重检验校正后，确定单个SNP和单个单倍型均与尿道下裂无关。为了在多个群体中评估这种关系，我们对六个SNP进行了荟萃分析，使用了我们目前的结果以及先前不同种族研究（包括1966例患者和2492例对照）的合并数据。六个SNP（rs1934179、rs4143304、rs9969978、rs1934188、rs7063116和rs1934190）与轻度/中度尿道下裂显著相关（OR>1，P<0.05），rs1934179与重度尿道下裂显著相关（OR>1，P<0.05）。
DGKK基因变异在中国汉族人群尿道下裂易感性中似乎不起主要作用。我们的荟萃分析支持了DGKK是尿道下裂常见风险基因的假设，特别是在白种人群体的轻度或中度尿道下裂病例中。
