Association of Human forkhead box protein 3 (FOXP3) gene polymorphisms with idiopathic recurrent pregnancy loss among Kazakhstani women

Abdukassimova, Meruyert; Kanabekova, Perizat; Bauyrzhanova, Zhansaya; Ukybassova, Talshyn; Kaldygulova, Lyazzat; Imankulova, Balkenzhe; Aimagambetova, Gulzhanat; Almawi, Wassim Y.

doi:10.1016/j.gene.2021.145835

Cited by 12 publications

(25 citation statements)

References 25 publications

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“…34,35 Similar to rs2294021, rs2232365 was also negatively associated with idiopathic RPL in Lebanese women. This was in sharp contrast to studies on Chinese Han, 27,32 Iranian, 26 Kazakhstani, 14 and North Indian 15,28,36 women. A recent meta-analysis involving 10 studies also concluded a positive association of rs2232365 minor allele and genotypes (A/G and G/G) with overall RPL risk.…”

Section: As Foxp3 Controls Treg Cells Development and Function And As...contrasting

confidence: 82%

“…We identified four single-nucleotide polymorphisms (SNPs) in FOXP3 gene (rs2294021, rs2232365, rs3761548, and rs141704699) that were reported to be clinically relevant by NCBI Entrez Gene SNP Geneview, and previous association with RPL. 14,25,26 FOXP3 genotyping was done by the VIC-and FAM-labeled allelic discrimination method, using assay-on-demand TaqMan assays (Applied Biosystems; Foster City, CA, USA). The tests were performed in 6-μl volume on QuantStudio 6/7 real-time PCR system (Applied Biosystems).…”

Section: Foxp3 Snp Genotypingmentioning

confidence: 99%

“…10,11 Considerable pieces of evidence indicated that pregnancy complications, including RPL, are associated with a reduced number and activity of Treg cells. 10,12 As the development and function of Treg cells is linked to the transcription factor forkhead box P3 (FOXP3), 13 a role for altered FOXP3 structure and expression in RPL pathogenesis was suggested, 10,12,14 evidenced by the finding that maternal rejection of the fetus as a semi-allograft results from a breakdown of tolerance, caused by defective FOXP3 signaling. 15 FOXP3 is encoded by FOXP3 (Scurfin) gene (Gene ID: 50943, MIM #300292), and acts both as an activator of transcription for Treg cells development, and as a transcriptional repressor in downregulating cytokine expression.…”

Section: Introductionmentioning

confidence: 99%

“…These include systemic lupus erythematosus, 18,19 Grave's disease, 20,21 type 1 (autoimmune) diabetes mellitus, and allergic rhinitis, 22,23 and pregnancy complications, including preeclampsia, 24,25 and RPL. 14,26 Insofar as FOXP3 expression is genetically inherited, several FOXP3 polymorphisms were reported to be associated with altered risk of RPL in Egyptian, Kazakhstani, 14 and North Indian 15 women. These include rs2232365 (−924 G>A) and rs3761548 (−3279 C>A), which were associated with RPL in Chinese Han, 27 Iranian, 26 and Palestinian (Gaza strip) subjects.…”

Section: Introductionmentioning

confidence: 99%

“…24 Recently, we documented a mixed association of rs2294021 (reduced risk), and rs2232365 (heightened risk) with RPL in Kazakhstani women. 14 As the differential association of FOXP3 variants with RPL is linked to the genetic background of a specific population, here we investigated the association of rs2294021, rs2232365, rs3761548, and rs141704699 FOXP3 variants with an altered incidence of RPL in a large cohort of Lebanese women with RPL.…”

Section: Introductionmentioning

confidence: 99%

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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

American J Rep Immunol

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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.

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Section: As Foxp3 Controls Treg Cells Development and Function And As...contrasting

confidence: 82%

Section: Foxp3 Snp Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

American J Rep Immunol

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Mouse Cre drivers: tools for studying disorders of the human female neuroendocrine-reproductive axis

Chemerinski

Liu

Morelli

et al. 2022

Biology of Reproduction

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Benign disorders of the human female reproductive system, such primary ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are associated with infertility and recurrent miscarriage, as well as increased risk of adverse health outcomes, including cardiovascular disease and type 2 diabetes. For many of these conditions, the contributing molecular and cellular processes are poorly understood. The overarching similarities between mice and humans have rendered mouse models irreplaceable in understanding normal physiology and elucidating pathological processes that underlie disorders of the female reproductive system. The utilization of Cre-LoxP recombination technology, which allows for spatial and temporal control of gene expression, has identified the role of numerous genes in development of the female reproductive system and in processes, such as ovulation and endometrial decidualization, that are required for the establishment and maintenance of pregnancy in mammals. In this comprehensive review, we provide a detailed overview of Cre drivers with activity in the neuroendocrine-reproductive axis that have been used to study disruptions in key intracellular signaling pathways. We first summarize normal development of the hypothalamus, pituitary, ovary, and uterus, highlighting similarities and differences between mice and humans. We then describe human conditions resulting from abnormal development and/or function of the organ. Finally, we describe loss-of-function models for each Cre driver that elegantly recapitulate some key features of the human condition and are associated with impaired fertility. The examples we provide illustrate use of each Cre driver as a tool for elucidating genetic and molecular underpinnings of reproductive dysfunction.

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Epidemiology of spontaneous pregnancy loss in Kazakhstan: A national population‐based cohort analysis during 2014–2019 using the national electronic healthcare system

Sakko,

Turesheva,

Gaipov

et al. 2023

Acta Obstet Gynecol Scand

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IntroductionSpontaneous pregnancy loss (SPL) is a common health problem that affects 1:10 of childbearing women, and is linked with physical and psychological complications. As the number of nationwide studies on the incidence of SPL is few, especially from middle‐income countries, in this study we investigated the epidemiology, complications and outcomes of SPL before 22 weeks of gestation by analyzing large‐scale healthcare data from the Unified Nationwide Electronic Healthcare System (UNEHS) in Kazakhstan.Material and methodsA population‐based study among women who experienced SPL in any healthcare setting of the Republic of Kazakhstan during the period of 2014–2019. The International Classification of Diseases (ICD) 10th edition and ICD 9th edition's procedural codes were utilized to retrieve data using relevant diagnostic and procedural codes.ResultsIn total, 207 317 records of women who have experienced an SPL before 22 weeks of gestation were analyzed from all Kazakhstani regions. The estimated prevalence of SPL was 8.7%, with a 20% decline over a 6‐year period. The SPL cases ratio comprises on average 6.2 per 1000 reproductive‐age women. Incomplete miscarriage (ICD‐10 code “O03.4”) was the most common type (37.8%), followed by blighted ovum (ICD‐10 code “O02.0”; 34.1%) and missed abortion (ICD‐10 code “O02.1”; 13.5%). The most common management methods were dilation and curettage of the uterus (ICD‐9 code “69.0”; 84.7%) and aspiration curettage of the uterus (ICD‐9 code “65.0”; 15%), whereas medical management was rarely performed (2.6%).ConclusionThe information available in UNEHS adequately identifies types of miscarriages and treatment methods. Although the prevalence of SPL before 22 weeks of gestation is decreasing, management of miscarriages requires closer attention.

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Association of Human forkhead box protein 3 (FOXP3) gene polymorphisms with idiopathic recurrent pregnancy loss among Kazakhstani women

Cited by 12 publications

References 25 publications

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

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

Mouse Cre drivers: tools for studying disorders of the human female neuroendocrine-reproductive axis

Epidemiology of spontaneous pregnancy loss in Kazakhstan: A national population‐based cohort analysis during 2014–2019 using the national electronic healthcare system

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