title: Association study of forkhead box P3 gene polymorphisms with unexplained recurrent spontaneous abortion.
abstract: Unexplained recurrent spontaneous abortion (URSA) has been suggested to be associated with the failure of fetal-maternal immunological tolerance in which the regulatory T lymphocytes (Tregs) play a crucial role. This study evaluated the association between single-nucleotide polymorphisms (SNPs) in the forkhead/winged helix transcription factor (FOXP3) gene, a key factor for the development and function of Tregs, and URSA, in an Iranian population. In this case-control study, 195 patients with a history of URSA and101 healthy women were included as case and control groups respectively. Four SNPs in the FOXP3 gene, two in the promoter region: -924A/G and -3279C/A, and two intronic, -20G/A and +459T/C, were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The -924A/G (p<0.0001) and -20G/A (p=0.008) polymorphisms were found to be associated with URSA. The respective odds ratios (OR) for bearing -924A/G and -20G/A gene polymorphisms were 4.1 [95% CI 2.3-7.5] and 2.1 [95% CI 1.2-3.6] fold higher in URSA women than those in controls. Thus, there were significant differences in the distribution of A and G alleles of -924A/G and -20G/A between URSA and controls (p=0.001, OR; 3.6 [95% CI 2.1-6.1] and p=0.006, OR; 1.6 [95% CI 1-2.6] respectively). No associations were found for -3279C/A and +459T/C polymorphisms between URSA and controls. These results suggest that polymorphisms of the FOXP3 gene might confer susceptibility to URSA, probably by altering FOXP3 function and/or its expression.
authors.affiliation: Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran; Department of Immunology, International Branch of Aras, Tabriz University of Medical Sciences, Tabriz, Iran; Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Naderi-Mahabadi
authors.affiliation: Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Zarei
authors.affiliation: Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Ramina
authors.initials: R
authors.lastname: Fatemi
authors.affiliation: Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Koorosh
authors.initials: K
authors.lastname: Kamali
authors.affiliation: Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Zhamak
authors.initials: Z
authors.lastname: Pahlavanzadeh
authors.affiliation: Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jeddi-Tehrani
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Tohid
authors.initials: T
authors.lastname: Kazemi
authors.affiliation: Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. Electronic address: F.Ideali@avicenna.ac.ir.
authors.forename: Farah
authors.initials: F
authors.lastname: Idali
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Forkhead box P3; Polymerase chain reaction-restriction fragment length polymorphism; Single-nucleotide polymorphism; Unexplained recurrent spontaneous abortion