Contribution of <i>JAK2</i> and <i>STAT3</i> Variants to the Genetic Susceptibility of Recurrent Spontaneous Miscarriage in a Tunisian Population

Messaoudi, Safia; Hizem, Sondes; Al-Sulaiti, Manar A; Al-Busaidi, Amna S; Magdoud, Kalthoum; Dendana, Maryam; Almawi, Wassim Y.; Mahjoub, Touhami

doi:10.1089/gtmb.2012.0201

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…These findings were consistent with the data conducted in the recent Chinese cohort (T allele: 65.63% and C allele: 34.37%) (Xie et al, 2013), suggesting that the SNP has homogeneity in the allele distribution among East-Asian (Thai and Chinese) populations. Interestingly, in contrast to our report, the frequency of C allele was higher than T allele in Tunisian Arabs (Middle East) (Messaoudi et al, 2013a;2013b). SNP rs1053004, localized on 3'-UTR of STAT3, regulates expression of STAT3 protein by altering mRNA degradation and decreased STAT3 activity (Foshay and Gallicano, 2009;Xie et al, 2013).…”

Section: Discussioncontrasting

confidence: 98%

Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

Chanthra

Payungporn²,

Chuaypen³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Section: Discussioncontrasting

confidence: 98%

Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

Chanthra

Payungporn²,

Chuaypen³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…43 Besides, Messaoudi et al, reported that the G allele in rs1053023 polymorphism is associated with recurrent miscarriages in Bahraini and Tunisian Arab populations. 44,45 This result was not surprising, as previous studies revealed higher levels of p-STAT3, IL17, and IL17R in patients with unexplained recurrent spontaneous abortions. 46,47 In another study evaluating the association between these two polymorphisms in STAT3 and the risk of developing noise-induced hearing loss (NIHL), it was demonstrated that the G allele in both variants was linked with NIHL risk.…”

Section: Discussionsupporting

confidence: 54%

Impact of miRNA-binding site polymorphisms in STAT3 gene on occurrence and clinical characteristics of systemic lupus erythematosus

Salehi

Sabet

Esmaeilzadeh³

et al. 2022

Lupus

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Background Signal transducer and activator of transcription 3 (STAT3) is a major regulator of immune response and chronic inflammatory conditions acting through regulation of B cells, T-helper 17 (Th17) cells, and IL-17 production. Previous studies have demonstrated that dysregulation of STAT3 is crucial for SLE pathogenesis and disease severity. It is believed that single nucleotide polymorphisms (SNPs) located at the 3′-UTR sequence of the target genes could dysregulate their expression by disrupting the binding site of miRNAs. In the present study, we assessed the possible association between rs1053005 and rs1053023 SNPs at miRNA binding sites in the STAT3 gene and the risk of SLE in the Iranian population for the first time. Methods 112 SLE cases and 120 healthy controls were genotyped for rs1053005 (A>G) and rs1053023 (A>G) polymorphisms in STAT3 using real-time PCR high resolution melting method (HRM). Results Our results revealed substantial associations between GG genotype and G allele of rs1053023 with enhanced risk of SLE (OR for GG genotype= 3.13; 95%CI [1.61–6.1], OR for G allele = 2.22; 95%CI [1.51–3.25]). However, no important correlations have been found between rs1053005 polymorphism and SLE susceptibility in this population ( p>0.05). Moreover, stratification analysis showed that these polymorphisms are correlated with parameters indicating disease activity and more severe course of the disease. These factors include some laboratory test results and clinical manifestations such as renal involvements. Conclusion The current study suggests a significant association between STAT3 polymorphisms and augmented risk of SLE, clinical symptoms, disease activity, and severity.

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“…Yang, H et al. [ 39 ] establish that mouse endometrium expressed CDKN2a gene during early pregnancy and it has a possible role in blastocyst implantation [ 39 ]. Inclusive mechanisms of CDKN2a in inducing apoptosis of the endometrial cells and contact with the other factors that influence the embryo blastocyst implantation required further research.…”

Section: Discussionmentioning

confidence: 99%

Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages

et al. 2018

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High androgen level impairs endometrial receptivity in women experiences the recurrent miscarriage. The mechanism of androgen actions on endometrium is still uncertain. We hypothesized that androgen has a direct effect on the endometrium in women with recurrent miscarriage. In the present study, we assess the impact of androgen (A2) at high concentration (10–7 M) on Ishikawa cells compared with the physiological concentration of androgen (10–9 M). To go into deeper analysis, we use global stable isotopes labeled profiling tactic using iTRAQ reagents, followed by 2D LC-MS/MS. We determine 175 non-redundant proteins, and 18 of these were quantified. The analysis of differentially expressed proteins (DEPs) identified 8 up-regulated proteins and 10 down-regulated in the high androgen group. These DEPs were examined by ingenuity pathway (IPA) analysis and established that these proteins might play vital roles in recurrent miscarriage and endometrium receptivity. In addition, proteins cyclin-dependent kinase inhibitor 2a (CDKN2a), endothelial protein C receptor (EPCR), armadillo repeat for velocardiofacial (ARVCF) were independently confirmed using western blot. Knockdown of CDKN2a significantly decreased the expression level of CDKN2a protein in ishikawa cells, and decreased migration (p < 0.01), invasion (p < 0.05), proliferation (p < 0.05), and the rate of Jar spheroid attachment (p < 0.05) to Ishikawa cell monolayer. The present results suggest that androgen at high concentration could alter the expression levels of proteins related to endometrium development and embryo implantation, which might be a cause of the impaired endometrial receptivity and miscarriage.

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Contribution of JAK2 and STAT3 Variants to the Genetic Susceptibility of Recurrent Spontaneous Miscarriage in a Tunisian Population

Abstract: STAT3 rs1053023, more so than the STAT3 rs1053004 or JAK2 rs2230724 polymorphisms, is associated with RSM risk.

Cited by 7 publications

References 38 publications

Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

Impact of miRNA-binding site polymorphisms in STAT3 gene on occurrence and clinical characteristics of systemic lupus erythematosus

Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages

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