Nan Liu, Yuping Yu, Ziying Chen, Jianbo Shu, Xiaofang Chen, Guodong Xu, Chunquan Cai
{"title":"Association of <i>IRX6</i> rs6499755 and <i>HAAO</i> rs3816183 Polymorphisms With Hypospadias Susceptibility in Northern Chinese Han Population.","authors":"Nan Liu, Yuping Yu, Ziying Chen, Jianbo Shu, Xiaofang Chen, Guodong Xu, Chunquan Cai","doi":"10.1155/genr/5775560","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> Hypospadias is one of the most common male congenital external genital malformation anomalies with unclear and multifactorial etiology. Our study aims to investigate whether <i>IRX6</i> rs6499755 and <i>HAAO</i> rs3816183 polymorphisms are susceptible to hypospadias in Chinese Northern Han. <b>Methods:</b> 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. <b>Results:</b> The risk allele [C] of <i>IRX6</i> rs6499755 was significantly associated with susceptibility to general hypospadias (OR = 1.547, <i>p</i>=0.01), anterior hypospadias (OR = 3.579, <i>p</i>=0.003) and posterior hypospadias (OR = 1.737, <i>p</i>=0.005). Besides, CC genotype carriers showed an increased risk of hypospadias compared with CT + TT carriers (OR = 1.832, <i>p</i>=0.026). The risk allele [T] of <i>HAAO</i> rs3816183 was associated with susceptibility to anterior/middle hypospadias (OR = 1.775, <i>p</i>=0.046). GMDR analysis revealed a significant interaction between <i>IRX6</i> rs6499755 and <i>HAAO</i> rs3816183 in the risk of hypospadias (cross-validation consistency = 10/10, testing balanced accuracy = 0.6065, <i>p</i>=0.0010). The results of meta-analysis (including 3789 cases and 9241 controls) indicated that <i>IRX6</i> rs6499755 and <i>HAAO</i> rs3816183 were significantly associated with hypospadias (both <i>p</i> < 0.00001). <b>Conclusions:</b> <i>IRX6</i> rs6499755 and <i>HAAO</i> rs3816183 polymorphisms were associated with hypospadias in Chinese Northern Han, and there is a potential interaction between <i>IRX6</i> rs6499755 and <i>HAAO</i> rs3816183 affecting the risk of hypospadias. The meta-analysis supported the hypothesis that <i>IRX6</i> rs6499755 and <i>HAAO</i> rs3816183 were the susceptibility loci for hypospadias. Further research is needed to clarify their pathogenic mechanisms.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2025 ","pages":"5775560"},"PeriodicalIF":1.4000,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181654/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1155/genr/5775560","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Association of IRX6 rs6499755 and HAAO rs3816183 Polymorphisms With Hypospadias Susceptibility in Northern Chinese Han Population.
Background: Hypospadias is one of the most common male congenital external genital malformation anomalies with unclear and multifactorial etiology. Our study aims to investigate whether IRX6 rs6499755 and HAAO rs3816183 polymorphisms are susceptible to hypospadias in Chinese Northern Han. Methods: 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. Results: The risk allele [C] of IRX6 rs6499755 was significantly associated with susceptibility to general hypospadias (OR = 1.547, p=0.01), anterior hypospadias (OR = 3.579, p=0.003) and posterior hypospadias (OR = 1.737, p=0.005). Besides, CC genotype carriers showed an increased risk of hypospadias compared with CT + TT carriers (OR = 1.832, p=0.026). The risk allele [T] of HAAO rs3816183 was associated with susceptibility to anterior/middle hypospadias (OR = 1.775, p=0.046). GMDR analysis revealed a significant interaction between IRX6 rs6499755 and HAAO rs3816183 in the risk of hypospadias (cross-validation consistency = 10/10, testing balanced accuracy = 0.6065, p=0.0010). The results of meta-analysis (including 3789 cases and 9241 controls) indicated that IRX6 rs6499755 and HAAO rs3816183 were significantly associated with hypospadias (both p < 0.00001). Conclusions:IRX6 rs6499755 and HAAO rs3816183 polymorphisms were associated with hypospadias in Chinese Northern Han, and there is a potential interaction between IRX6 rs6499755 and HAAO rs3816183 affecting the risk of hypospadias. The meta-analysis supported the hypothesis that IRX6 rs6499755 and HAAO rs3816183 were the susceptibility loci for hypospadias. Further research is needed to clarify their pathogenic mechanisms.
期刊介绍：
Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.
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