The serum level of transforming growth factor beta1 and its association with Foxp3 gene polymorphism in Iranian women with recurrent spontaneous abortion

Problem: Fork Head Box Protein 3 (FOXP3) is an X‐linked gene, codes for a master transcription regulatory protein that controls the development and function of immunosuppressive T regulatory (Treg) cells. They are crucial mediators of maternal foetal tolerance and successful pregnancy outcome. The aim of the study is to evaluate the association of FOXP3 rs3761548 functional polymorphism and to assess the serum concentrations of full‐length FOXP3 protein in Unexplained Recurrent Spontaneous Abortions (URSA) patients of Southern India. Method of study: The study included blood samples from 150 URSA patients and 150 healthy, pregnant parous women. Polymerase Chain Reaction‐Restriction Fragment Length Polymorphism was done for rs3761548 FOXP3 genotyping. Serum concentrations of full‐length FOXP3 protein were estimated by enzyme‐linked immunosorbent assay. Results: The frequencies of mutant A allele, CA and AA genotypes of rs3761548 functional polymorphism were significantly elevated in patients compared to healthy, pregnant parous women and exhibited a two, three and twofold increased risk respectively towards URSA. Serum concentrations of full‐length FOXP3 protein were high in controls compared to patients (10.14 ± .30 vs. 8.84 ± 1.73 ng/ml; p < .05). Conclusion: Our results advocate an association of FOXP3 rs3761548 polymorphism and reduced expression of full‐length FOXP3 protein with URSA.

Section: Discussionmentioning

confidence: 96%

Association of FOXP3 rs3761548 polymorphism and its reduced expression with unexplained recurrent spontaneous abortions: A South Indian study

Dirsipam

Ponnala

Madduru

et al. 2021

“…In conclusion, our study indicates that variation in FOXP3 gene is associated with a reduced risk of RPL among Lebanese women. The study has notable strengths, specifically because idiopathic RPL cases and control women were ethnically juxtaposed, thus reducing the contribution of ethnicity, which is of concern in view of the ethnic structure of the contemporary Lebanese population, 41–43 and in the robust statistical analysis, with adjustment for some confounding variables. Our study has also some limitations in that we did not evaluate Foxp3 protein concentrations against the studied variants.…”

Section: Discussionmentioning

confidence: 99%

Human forkhead box protein 3 gene variants associated with altered susceptibility to idiopathic recurrent pregnancy loss: A retrospective case‐control study

Bahia

Zitouni

Kanabekova

et al. 2022

Background The pathogenesis of recurrent pregnancy loss (RPL) is multifactorial and not completely elucidated. Dysregulated immunity was implicated with RPL, in which regulatory T cells (Tregs) are key. As Tregs development and function are regulated by forkhead box P3 (FOXP3) transcription factor, and as FOXP3 expression is genetically determined, a role for FOXP3 polymorphisms in RPL pathogenesis was suggested. Aim To investigate the association of rs2294021, rs2232365, rs3761548, and rs141704699 FOXP3 variants with idiopathic RPL in Lebanese women. Methods This retrospective case‐control study included 386 RPL cases and 398 age‐matched control women. Logistic odds ratios (OR) were estimated with 95% confidence interval after adjustment; a significance value of P<.05 was set. Results Significantly lower rs22944021 and rs2232365 minor allele frequency (MAF) was found in patients with idiopathic RPL in comparison with the control group. Furthermore, statistically significantly lower frequency of heterozygous and homozygous rs2294021 and rs2232365 genotypes was seen in controls, while significantly lower rs3761548 heterozygous genotype frequencies were found in the patient group. Obesity, antihypertension treatment, smoking, positive RPL family history, abortion state, and infertility treatment correlated negatively with rs2294021, while rs2232365 negatively correlated with obesity, and rs3761548 negatively correlated with infertility treatment. Marked linkage disequilibrium (LD) was noted among FOXP3 SNPs, with TGCC and CGAC haplotypes being positive, while CAAC, CACC, and TGAC haplotypes being negatively associated with RPL risk. Except for CGAC, the association of these haplotypes with RPL persisted after adjustment. Conclusion FOXP3 gene variants and haplotypes are associated with altered incidence of RPL, proposing the role of Treg in RPL pathogenesis.

“…Additionally, Tregs also suppress the responses of cytotoxic T cells, natural killer (NK) cells, and NK‐T cells against both self‐antigens and allogenic paternal antigens associated with pregnancy disorders and rejection 19,20 . As a result, FOXP3 has important effects on immune response and development of certain immune‐related pregnancy complications including PE 25,26,36 . For instance, loss of FOXP3 expression was reported to lead to the inability of Tregs to suppress the immune response, which ultimately affected the development of PE 18,37–39 .…”

Section: Discussionmentioning

confidence: 99%

“…The FOXP3 gene is located on human X‐chromosome at p11.23, contains 11 exons and 10 introns and encodes a 431 amino‐acid protein with a molecular weight of 47.25 kD 11 . FOXP3 is highly polymorphic in various regions (i.e., promoter, intron and exon regions) and its polymorphisms were reported to be associated with susceptibility and development of certain pregnancy abnormalities including recurrent spontaneous abortion (RSA), infertility with and without endometriosis and PE as well 11,25,26 . Recently, growing researches investigated the relationship of FOXP3 polymorphisms with PE risk, among which single nucleotide polymorphisms (SNPs) of ‐3279C/A (rs3761548), ‐925A/G (rs2232365), rs4824747, ‐3499T/C (rs3761547) and IVS9+459T/C (rs2280883) were mostly investigated 9–11,27–31 .…”

Section: Introductionmentioning

confidence: 99%

Associations of FOXP3 gene polymorphisms with susceptibility and severity of preeclampsia: A meta‐analysis

Fan

Yin³

et al. 2022

Objective FOXP3 single nucleotide polymorphisms (SNPs) were recently elucidated to influence the development of preeclampsia (PE), but the results on this issue still remained controversial. Thus, a meta‐analysis was implemented to systematically investigate the roles of FOXP3 SNPs in PE. Methods Eligible publications were identified by retrieving relevant electronic databases. Meanwhile, the association intensity was estimated by calculating odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models. Results Totally eight investigations involving 3446 subjects were enrolled in the final meta‐analysis. The AC and AC + CC genotypes of FOXP3 rs3761548 were related to the susceptibility of PE in over‐dominant (OR = 1.19, 95%CI = 1.02‐1.38, P = 0.03) and recessive (OR = 0.59, 95% CI: 0.36‐0.97, P = 0.04) models. Furthermore, correlation between rs2232365 and PE was observed in recessive model (GG vs. GA + AA) (OR = 0.79, 95%CI: 0.65‐0.97, P = 0.03). Moreover, rs2232365 GA and GG + GA genotypes were associated with the severity of PE. However, rs4824747, rs3761547 and rs2280883 polymorphisms had no significant impact on PE susceptibility. Conclusions FOXP3 rs3761548 and rs2232365 SNPs influenced the PE susceptibility and therefore may be potential biomarkers for prediction of PE risk.