Study of the association of forkhead box P3 (FOXP3) gene polymorphisms with unexplained recurrent spontaneous abortions in Indian population. 2018

Shivani Mishra, and Anukool Srivastava, and Kausik Mandal, and Shubha R Phadke
Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India. shubharaophadke@gmail.com.

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.

UI MeSH Term Description Entries
D007194 India A country in southern Asia, bordering the Arabian Sea and the Bay of Bengal, between Burma and Pakistan. The capitol is New Delhi. Republic of India
D007438 Introns Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes. Intervening Sequences,Sequences, Intervening,Intervening Sequence,Intron,Sequence, Intervening
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011401 Promoter Regions, Genetic DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D005260 Female Females
D005787 Gene Frequency The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION. Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000026 Abortion, Habitual Three or more consecutive spontaneous abortions. Abortion, Recurrent,Miscarriage, Recurrent,Recurrent Early Pregnancy Loss,Habitual Abortion,Habitual Abortions,Recurrent Abortion,Recurrent Abortions,Recurrent Miscarriage,Recurrent Miscarriages
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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