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  • Title: Study of the association of forkhead box P3 (FOXP3) gene polymorphisms with unexplained recurrent spontaneous abortions in Indian population.
    Author: Mishra S, Srivastava A, Mandal K, Phadke SR.
    Journal: J Genet; 2018 Jun; 97(2):405-410. PubMed ID: 29932060.
    Abstract:
    Recurrent spontaneous abortions (RSA) is defined as three or more consecutive pregnancy losses before 20 weeks of gestation. Various causes of RSA have been identified, still 50% cases remain unexplained after evaluation. One of the causes of unexplained recurrent spontaneous abortions (URSA) is supposed to be the disruption of immunological tolerance at foeta-maternal interface. Regulatory T cells (Tregs) are responsible for the development of immune-tolerant environment at foetal-maternal interface and supports pregnancy. Forkhead/winged helix transcription factor (FOXP3) gene plays an important role in the development and function of Tregs. In URSA, Tregs (CD4+CD25+) are reduced in peripheral blood and decidua of pregnant women. This reduction of Tregs (CD4+CD25+) is associated with decreased expression of FOXP3 gene. This study evaluated the association between singlenucleotide polymorphisms (SNPs) in FOXP3 gene and URSA in Indian population. In this study, 100 patients with a history of URSA and 100 healthy ethnically matched women with at least one normal pregnancy and no abortion were included as case and control groups, respectively. Four SNPs of FOXP3 gene, two in the promoter region: -924A/G and -3279C/A, and two intronic, -20G/A and +459T/C, were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). -924A/G and +459T/C polymorphisms were found to be associated with URSA. -3279C/A and -20G/A polymorphism were not found to be associated with URSA. The odds ratio (OR) of mutant allele G for -924A/G polymorphism was 2.5 (95% CI 1.7-3.8; P< 0.001) and mutant allele C for +459T/C polymorphism was 1.7 (95% CI 1.1-2.6; P= 0.01). For -20G/A polymorphism, only GG genotype was found in both URSA and controls. These results suggest that -924A/G and +459T/C polymorphisms of the FOXP3 gene might be associated with URSA and -20G/A polymorphism is likely to be rare in Indian population and might not be associated with URSA.
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