title: Interaction between TP63 and MDM2 genes and the risk of recurrent pregnancy loss.
abstract: OBJECTIVE
  Recent studies have investigated the role of the p53 gene family in reproductive processes. Each member of the gene family acts through different mechanisms: p53 is involved in genomic stability and regulation of blastocyst implantation; p63 acts as a regulator of the quality and maturation of oocytes; and p73 controls the meiotic spindle. Polymorphisms in the genes of the p53 family have been associated with female infertility. One polymorphism in MDM2, the main regulator of the p53 family, has also been associated with this condition. Although polymorphisms in the TP53 gene have been related to recurrent pregnancy loss (RPL), there have been no studies associating polymorphisms in p63 and p73 with RPL. Therefore, the aim of this study was to evaluate the role of polymorphisms in the TP63 (rs17506395), TP73 (rs2273953, rs1801173), and MDM2 (SNP309, rs2279744) genes as risk factors for RPL.
  
  
  METHODS
  A case-control study was conducted in 153 women with RPL and 143 fertile women with at least two living children and no history of pregnancy loss. Molecular analysis was performed by TaqMan Allelic Discrimination assay. The statistical analysis was performed using SPSS software version 20.0 and the chi-square test, Student's t-test, Mann-Whitney test and logistic regression to compare the evaluated characteristics between both groups and RPL outcome.
  
  
  RESULTS
  The allelic and genotypic frequencies did not differ between the groups when analyzed separately, however, the interaction between the TP63 TT and MDM2 TT genotypes was shown to increase the risk of RPL (OR=2.19, CI 95%: 1.28-3.75, p=0.004), even when adjusted for alcohol consumption, smoking, number of pregnancies and ethnicity (OR=1.97, CI 95%: 1.27-3.58, p=0.025).
  
  
  CONCLUSIONS
  Our results suggest that genes from the p53 family proteins, evaluated here, have an influence on the risk of RPL.
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil.
authors.forename: Lucas R
authors.initials: LR
authors.lastname: Fraga
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil.
authors.forename: Juliano A
authors.initials: JA
authors.lastname: Boquett
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil.
authors.forename: Caroline G
authors.initials: CG
authors.lastname: Dutra
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil; INAGEMP - Instituto Nacional de Genética Médica Populacional, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil; Postgraduate Program in Epidemiology. Universidade Federaldo Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Vianna
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Heck
authors.affiliation: Post-Graduation Program in Biotechnology in Health and Investigative Medicine and Department of Obstetrics, Gynecology and Human Reproduction, Medical School, Universidade Federal da Bahia (UFBA), Salvador 40110-100, Brazil.
authors.forename: Rozana O
authors.initials: RO
authors.lastname: Gonçalves
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil.
authors.forename: Diego D
authors.initials: DD
authors.lastname: Paskulin
authors.affiliation: Post-Graduation Program in Biotechnology in Health and Investigative Medicine and Department of Obstetrics, Gynecology and Human Reproduction, Medical School, Universidade Federal da Bahia (UFBA), Salvador 40110-100, Brazil.
authors.forename: Olívia L
authors.initials: OL
authors.lastname: Costa
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil; INAGEMP - Instituto Nacional de Genética Médica Populacional, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Ashton-Prolla
authors.affiliation: INAGEMP - Instituto Nacional de Genética Médica Populacional, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil.
authors.forename: Maria Teresa V
authors.initials: MT
authors.lastname: Sanseverino
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil; INAGEMP - Instituto Nacional de Genética Médica Populacional, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil. Electronic address: lavinia.faccini@ufrgs.br.
authors.forename: Lavínia
authors.initials: L
authors.lastname: Schuler-Faccini
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: MDM2; Recurrent pregnancy loss; TP63; TP73; p53 family proteins