title: p53 signaling pathway polymorphisms associated to recurrent pregnancy loss.
abstract: The p53 protein is known for performing essential functions in the maintenance of genomic stability in somatic cells and prevention of tumor formation. Studies of the p53 signaling pathway have suggested associations between some polymorphisms and infertility, post-in vitro fertilization implantation failure and recurrent abortions. The TP53 Pro72Arg polymorphism has been implicated as a risk factor for recurrent pregnancy loss (RPL); however, the association is controversial. In this study, our objective was to evaluate selected polymorphisms in genes of the p53 signalling pathway [TP53 c.215G>C (Pro72Arg), MDM2 c.14+309T>G (SNP309) and LIF c.1414T>G in the region 3' UTR] and determine their effect as risk factors for RPL. In a case-control study, we investigated 120 women with two or more pregnancy losses and 143 fertile control women reporting at least two live births and no history of pregnancy loss. When analyzed separately, the allele and genotype distributions of the polymorphisms in the two groups were not different. However, in a multivariate analysis adjusted for alcohol consumption, smoking, ethnicity, and number of pregnancies, the interaction between the genotypes TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) showed to be associated to RPL, increasing the risk for this condition (OR = 2.58, 95% CI: 1.31-5.07, p = 0.006). In conclusion, our study indicates that the combination of TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) genotypes may be a risk factor for RPL.
authors.affiliation: Post-Graduation Program in Genetics and Molecular Biology, Departament of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Caixa Postal 15031 - Agencia Campus UFRGS, Porto Alegre, RS, 91501-970, Brazil, lucas_r_fraga@hotmail.com.
authors.forename: L R
authors.initials: LR
authors.lastname: Fraga
authors.forename: C G
authors.initials: CG
authors.lastname: Dutra
authors.forename: J A
authors.initials: JA
authors.lastname: Boquett
authors.forename: F S L
authors.initials: FS
authors.lastname: Vianna
authors.forename: R O
authors.initials: RO
authors.lastname: Gonçalves
authors.forename: D D
authors.initials: DD
authors.lastname: Paskulin
authors.forename: O L
authors.initials: OL
authors.lastname: Costa
authors.forename: P
authors.initials: P
authors.lastname: Ashton-Prolla
authors.forename: M T V
authors.initials: MT
authors.lastname: Sanseverino
authors.forename: L
authors.initials: L
authors.lastname: Schuler-Faccini
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D016022:Case-Control Studies; D005006:Ethnicity; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2