title: A functional variant in the UBE2B gene promoter is associated with idiopathic azoospermia.
abstract: BACKGROUND
  A variety of genetic variants lead to abnormal human spermatogenesis. The ubiquitin-conjugating enzyme E2B (UBE2B) plays a significant role in spermatogenesis as Ube2b-knockout male mice are infertile.
  
  
  METHODS
  In this study, we sequenced the exon and promoter region of UBE2B in 776 patients diagnosed with idiopathic azoospermia (IA) and 709 proven fertile men to examine whether UBE2B is involved in the pathogenesis of IA.
  
  
  RESULTS
  In the exon region, two novel synonymous variants were detected in the patient group. In the promoter region, four known variants and four novel variants were identified in the patient group. Of the novel variants in the promoter region, three were located at the binding site of specificity protein 1 (SP1) transcription factor analyzed by TRANSFAC software. Luciferase assays demonstrated that one heterozygous variant (Chr5.133706925 A > G) inhibited the transcriptional regulation activity of SP1.
  
  
  CONCLUSIONS
  A novel variant (Chr5.133706925 A > G) residing in the UBE2B gene promoter region confers a high risk for IA in a Chinese population. These results support a role for UBE2B in the pathogenesis of IA.
authors.affiliation: Shenzhen Domesticated Organ Medical Engineering Research and Development Center, First Affiliated Hospital of Shenzhen University, Shenzhen, China. molly__molly@163.com.|Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Biomedical Research Institute, Shenzhen PKU-HKUST Medical Center, Shenzhen, China. molly__molly@163.com.
authors.forename: Lisha
authors.initials: L
authors.lastname: Mou
authors.affiliation: Shenzhen Domesticated Organ Medical Engineering Research and Development Center, First Affiliated Hospital of Shenzhen University, Shenzhen, China. zhangqiang2131617@163.com.|The people's hospital of Ankang, Shanxin, China. zhangqiang2131617@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Shenzhen Domesticated Organ Medical Engineering Research and Development Center, First Affiliated Hospital of Shenzhen University, Shenzhen, China. diaodiao005@163.com.
authors.forename: Ruiying
authors.initials: R
authors.lastname: Diao
authors.affiliation: Shenzhen Domesticated Organ Medical Engineering Research and Development Center, First Affiliated Hospital of Shenzhen University, Shenzhen, China. caizhiming2000@163.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Biomedical Research Institute, Shenzhen PKU-HKUST Medical Center, Shenzhen, China. guiyaoting2007@aliyun.com.
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D053713:Azoospermia / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013091:Spermatogenesis / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*; D055815:Young Adult
chemical_list: C471546:UBE2B protein, human; D044763:Ubiquitin-Conjugating Enzymes