Liu Nan, Yu Yuping, Chen Ziying, Shu Jianbo, Chen Xiaofang, Xu Guodong, Cai Chunquan
Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin 300134, China.
Tianjin Pediatric Research Institute, Tianjin 300134, China.
Genet Res (Camb). 2025 Jun 13;2025:5775560. doi: 10.1155/genr/5775560. eCollection 2025.
Hypospadias is one of the most common male congenital external genital malformation anomalies with unclear and multifactorial etiology. Our study aims to investigate whether rs6499755 and rs3816183 polymorphisms are susceptible to hypospadias in Chinese Northern Han. We enrolled 113 patients with hypospadias and 182 healthy controls in the case-control study. Genotyping of single nucleotide polymorphisms (SNPs) was performed using High Resolution Melting (HRM). 113 hypospadias cases were further divided into anterior, middle and posterior subgroups for analysis. In addition, we performed a meta-analysis to evaluate the relationship in multiple populations. The risk allele [C] of rs6499755 was significantly associated with susceptibility to general hypospadias (OR = 1.547, =0.01), anterior hypospadias (OR = 3.579, =0.003) and posterior hypospadias (OR = 1.737, =0.005). Besides, CC genotype carriers showed an increased risk of hypospadias compared with CT + TT carriers (OR = 1.832, =0.026). The risk allele [T] of rs3816183 was associated with susceptibility to anterior/middle hypospadias (OR = 1.775, =0.046). GMDR analysis revealed a significant interaction between rs6499755 and rs3816183 in the risk of hypospadias (cross-validation consistency = 10/10, testing balanced accuracy = 0.6065, =0.0010). The results of meta-analysis (including 3789 cases and 9241 controls) indicated that rs6499755 and rs3816183 were significantly associated with hypospadias (both < 0.00001). rs6499755 and rs3816183 polymorphisms were associated with hypospadias in Chinese Northern Han, and there is a potential interaction between rs6499755 and rs3816183 affecting the risk of hypospadias. The meta-analysis supported the hypothesis that rs6499755 and rs3816183 were the susceptibility loci for hypospadias. Further research is needed to clarify their pathogenic mechanisms.
尿道下裂是最常见的男性先天性外生殖器畸形之一，其病因不明且具有多因素性。我们的研究旨在调查rs6499755和rs3816183基因多态性是否易导致中国北方汉族人群患尿道下裂。在这项病例对照研究中，我们纳入了113例尿道下裂患者和182名健康对照者。使用高分辨率熔解曲线分析（HRM）对单核苷酸多态性（SNP）进行基因分型。113例尿道下裂病例进一步分为前部、中部和后部亚组进行分析。此外，我们进行了荟萃分析以评估多人群中的关系。rs6499755的风险等位基因[C]与一般尿道下裂易感性（OR = 1.547，P = 0.01）、前部尿道下裂（OR = 3.579，P = 0.003）和后部尿道下裂（OR = 1.737，P = 0.005）显著相关。此外，与CT + TT携带者相比，CC基因型携带者患尿道下裂的风险增加（OR = 1.832，P = 0.026）。rs3816183的风险等位基因[T]与前部/中部尿道下裂易感性相关（OR = 1.775，P = 0.046）。多基因疾病遗传易感性分析（GMDR）显示rs6499755和rs3816183在尿道下裂风险中存在显著相互作用（交叉验证一致性 = 10/10，测试平衡准确率 = 0.6065，P = 0.0010）。荟萃分析结果（包括3789例病例和9241名对照）表明，rs6499755和rs3816183与尿道下裂显著相关（两者P均<0.00001）。rs6499755和rs3816183基因多态性与中国北方汉族人群的尿道下裂相关，并且rs6499755和rs3816183之间存在潜在相互作用影响尿道下裂风险。荟萃分析支持rs6499755和rs
