title: Associations of Polymorphisms in WNT9B and PBX1 with Mayer-Rokitansky-Küster-Hauser Syndrome in Chinese Han.
abstract: BACKGROUND
  Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare syndrome that is characterized by congenital aplasia of the uterus and the upper portion (2/3) of the vagina. Previous attempts to identify causal mutations of MRKH syndrome have primarily resulted in negative outcomes. We investigated whether these reported variants are associated with MRKH syndrome (types I and II) in a relatively large sample size of Chinese Han patients, and whether any gene-gene epistatic interactions exist among these variants.
  
  
  METHODS
  This study included 182 unrelated Chinese women with MRKH syndrome (155 with type I and 27 with type II) and 228 randomized female controls. Seventeen candidate loci in the AMH, PBX1, WNT4, WNT7A, WNT9B, HOXA10, HOXA11, LHXA1 and GALT genes were genotyped using the Sequenom MassARRAY iPLEX platform. Single-marker association, additive effects and multifactor interactions were investigated.
  
  
  RESULTS
  The gene frequency distributions of MRKH type 1 and type 2 were similar. Rs34072914 in WNT9B was found to be associated with MRKH syndrome (P = 0.024, OR = 2.65, 95%CI = 1.14-6.17). The dominant models of rs34072914 and rs2275558 in WNT9B and PBX1, respectively, were significantly associated with MRKH syndrome risk in the Chinese Han patients. Additive gene-gene interaction analyses indicated a significant synergetic interaction between WNT9B and PBX1 (RERI = 1.397, AP = 0.493, SI = 4.204). Multifactor dimensionality reduction (MDR) analysis revealed novel dimensional epistatic four-gene effects (AMH, PBX1, WNT7A and WNT9B) in MRKH syndrome.
  
  
  CONCLUSIONS
  This association study successfully identified two susceptibility SNPs (WNT9B and PBX1) associated with MRKH syndrome risk, both separately and interactively. The discovery of a four-gene epistatic effect (AMH, PBX1, WNT7A and WNT9B) in MRKH syndrome provides novel information for the elucidation of the genetic mechanism underlying the etiology of MRKH syndrome.
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Tiefen
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000175:diagnosis / Q000235:genetics*; D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D000595:Amino Acid Sequence; D054304:Anti-Mullerian Hormone / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D000013:Congenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D009095:Mullerian Ducts / Q000002:abnormalities*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016415:Sequence Alignment; D014599:Uterus / Q000002:abnormalities / Q000473:pathology; D014621:Vagina / Q000002:abnormalities / Q000473:pathology; D051153:Wnt Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C092778:WNT7A protein, human; C449090:WNT9B protein, human; D051153:Wnt Proteins; C083400:PBX1 protein, human; D054304:Anti-Mullerian Hormone