Bin Zhou1, Tielong Tang2, Peng Chen3, Yan Pu3, Mingfu Ma4, Danyan Zhang4, Lianbing Li4, Peng Zhang5, Yaping Song1, Lin Zhang6. 1. Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, PR China. 2. Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, PR China. 3. Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, PR China. 4. Key Laboratory of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing 400020, PR China; Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020, PR China. 5. Department of Urology, West China Hospital, Sichuan University, Chengdu, PR China. 6. Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, PR China; Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, PR China. Electronic address: zhanglin@scu.edu.cn.
Abstract
BACKGROUND: Cryptorchidism is one of the most common congenital anomalies in newborn boys. Although the mechanism responsible for the pathophysiology of cryptorchidism has not yet been well addressed, the Wnt signaling pathway has been involved in the development of cryptorchidism. Axin1 is a central component of the Wnt signaling pathway and may play a critical role in the development of cryptorchidism. OBJECTIVE: We assumed that cryptorchidism risk and the AXIN1 gene may have an association. Thus we picked out three tag SNPs (single nucleotide polymorphisms) in the AXIN1 gene and aimed to investigate whether cryptorchidism risk is associated with polymorphisms in the AXIN1 gene. STUDY DESIGN: The variants were discriminated using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methods. A total of 113 cases and 179 controls were recruited to participate in this study, including 92 unilateral cryptorchidism and 21 bilateral cases. In bilateral cases, the position of the testis was decided by the higher one. RESULTS: A significantly increased cryptorchidism risk was found to be associated with both the T allele (p = 2e(-4), OR 1.96, 95% CI 1.37-2.78) and T/T genotype (p = 6e(-4), OR 4.00, 95% CI 1.79-9.09) of rs370681 polymorphism, and, compared with the C/C genotype, a significantly increased cryptorchidism risk was associated with the C/T-T/T genotype (p = 4e(-4), OR 2.44, 95% CI 1.47-4.00) of rs370681 polymorphisms. DISCUSSION: Among the three tag SNPs we have chosen in AXIN1, two SNPs are located in the intron region, the other SNP is located in the synonymous codon region. Evidential research has indicated that introns and other non-protein-coding RNAs may have evolved to function as network control molecules in higher organisms. Therefore, we suspected that the tag SNPs may work as controls influencing the conduct of other genes rather than affecting the structure of the protein by influencing the coding of amino acid. There were limitations in our study. One is that we did not test the expression level of Axin1. Secondly, the number of the study subjects is limited. Finally, the molecular mechanisms by which AXIN1 is involved in susceptibility to cryptorchidism should be characterized. CONCLUSIONS: We assessed the impact of the genetic variability of the AXIN1 gene on cryptorchidism. We have offered primary evidence that the T allele and T/T genotype of rs370681 polymorphisms and C/T genotype of rs1805105 polymorphisms in AXIN1 gene are more frequent in patients with cryptorchidism.
BACKGROUND: Cryptorchidism is one of the most common congenital anomalies in newborn boys. Although the mechanism responsible for the pathophysiology of cryptorchidism has not yet been well addressed, the Wnt signaling pathway has been involved in the development of cryptorchidism. Axin1 is a central component of the Wnt signaling pathway and may play a critical role in the development of cryptorchidism. OBJECTIVE: We assumed that cryptorchidism risk and the AXIN1 gene may have an association. Thus we picked out three tag SNPs (single nucleotide polymorphisms) in the AXIN1 gene and aimed to investigate whether cryptorchidism risk is associated with polymorphisms in the AXIN1 gene. STUDY DESIGN: The variants were discriminated using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methods. A total of 113 cases and 179 controls were recruited to participate in this study, including 92 unilateral cryptorchidism and 21 bilateral cases. In bilateral cases, the position of the testis was decided by the higher one. RESULTS: A significantly increased cryptorchidism risk was found to be associated with both the T allele (p = 2e(-4), OR 1.96, 95% CI 1.37-2.78) and T/T genotype (p = 6e(-4), OR 4.00, 95% CI 1.79-9.09) of rs370681 polymorphism, and, compared with the C/C genotype, a significantly increased cryptorchidism risk was associated with the C/T-T/T genotype (p = 4e(-4), OR 2.44, 95% CI 1.47-4.00) of rs370681 polymorphisms. DISCUSSION: Among the three tag SNPs we have chosen in AXIN1, two SNPs are located in the intron region, the other SNP is located in the synonymous codon region. Evidential research has indicated that introns and other non-protein-coding RNAs may have evolved to function as network control molecules in higher organisms. Therefore, we suspected that the tag SNPs may work as controls influencing the conduct of other genes rather than affecting the structure of the protein by influencing the coding of amino acid. There were limitations in our study. One is that we did not test the expression level of Axin1. Secondly, the number of the study subjects is limited. Finally, the molecular mechanisms by which AXIN1 is involved in susceptibility to cryptorchidism should be characterized. CONCLUSIONS: We assessed the impact of the genetic variability of the AXIN1 gene on cryptorchidism. We have offered primary evidence that the T allele and T/T genotype of rs370681 polymorphisms and C/T genotype of rs1805105 polymorphisms in AXIN1 gene are more frequent in patients with cryptorchidism.
Authors: Jason K Gurney; Katherine A McGlynn; James Stanley; Tony Merriman; Virginia Signal; Caroline Shaw; Richard Edwards; Lorenzo Richiardi; John Hutson; Diana Sarfati Journal: Nat Rev Urol Date: 2017-06-27 Impact factor: 14.432
Authors: George Andrei Crauciuc; Mihaela Iancu; Peter Olah; Florin Tripon; Mădălina Anciuc; Liliana Gozar; Rodica Togănel; Claudia Bănescu Journal: Int J Environ Res Public Health Date: 2020-10-21 Impact factor: 3.390