title: The variations in the AXIN1 gene and susceptibility to cryptorchidism.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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: 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.
authors: Bin
authors: B
authors: Zhou
authors: Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, PR China.
authors: Tielong
authors: T
authors: Tang
authors: Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, PR China.
authors: Peng
authors: P
authors: Chen
authors: Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, PR China.
authors: Yan
authors: Y
authors: Pu
authors: 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.
authors: Mingfu
authors: M
authors: Ma
authors: 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.
authors: Danyan
authors: D
authors: Zhang
authors: 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.
authors: Lianbing
authors: L
authors: Li
authors: Department of Urology, West China Hospital, Sichuan University, Chengdu, PR China.
authors: Peng
authors: P
authors: Zhang
authors: 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.
authors: Yaping
authors: Y
authors: Song
authors: 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.
authors: Lin
authors: L
authors: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics*; D060466:Axin Protein / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D003456:Cryptorchidism / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein
keywords: AXIN1; Association; Cryptorchidism; Polymorphisms