High mobility group box 1 protein polymorphism affects susceptibility to recurrent pregnancy loss by up-regulating gene expression in chorionic villi

Hua, Jing; Wu, Jie; Yang, Qi; Cai, Yan; He, Wenxiu; Liu, Cuiying

doi:10.1007/s10815-015-0493-3

Cited by 18 publications

(16 citation statements)

References 21 publications

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“…However, how the SNPs in the HMGB1 gene influenced the progression of disorders is unclear. A study based on clinical samples reported that patients with rs2249825 GG genotype had significantly elevated levels of HMGB1 in chorionic villi compared to those with CG or CC genotype [ 33 ]. In the present study, we found that only SNP rs2249825 was associated with CRC incidence.…”

Section: Discussionmentioning

confidence: 99%

Association of HMGB1 Gene Polymorphisms with Risk of Colorectal Cancer in a Chinese Population

Wang

Bei

et al. 2016

Med Sci Monit

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BackgroundColorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. More advanced work is required in the detection of biomarkers for CRC susceptibility and prognosis. High-mobility group box-1 (HMGB1) is an angiogenesis-related gene reported to be associated with the development of CRC. The direct evidence of HMGB1 gene polymorphisms as biomarkers for CRC has not been reported previously.Material/MethodsA total of 240 CRC patients and 480 healthy controls were periodically enrolled. DNA was extracted from blood specimens. The distributions of SNPs of HMGB1 were determined by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay.ResultsIn this case-control study, we observed a significant association between overall CRC risk and SNP rs2249825 (CG vs. CC and GG vs. CC). Participants carrying both rs2249825 CG (OR, 2.67; 95% CI, 1.89 to 3.78) and rs2249825 GG genotypes (OR, 2.32; 95% CI, 1.13 to 4.73) had a significantly increased risk of developing CRC compared to those carrying GG genotype. rs2249825 was associated with the risk of CRC in the dominant model but not in the recessive model. However, we found no significant differences in the rs1412125 or rs1045411 polymorphisms in the HMGB1. Advanced analyses showed that the number of rs2249825 G alleles showed a significant relationship with risk of CRC.ConclusionsOur results show an association between HMGB1 rs2249825 SNP and CRC incidence in the Chinese Han population. However, population-based studies with more subjects and prognostic effects are needed to verify the association of HMGB1 SNPs with CRC susceptibility, severity, and long-term prognosis.

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Section: Discussionmentioning

confidence: 99%

Association of HMGB1 Gene Polymorphisms with Risk of Colorectal Cancer in a Chinese Population

Wang

Bei

et al. 2016

Med Sci Monit

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“…This is plausible, as T reg cells are known to regulate the maternal response to the fetus in normal pregnancy, and a dearth of them could therefore lead to an overactive immune response (from T H 17 cells as well as other immune actors) that would result in pregnancy loss. Other literature points to upregulated activity of the HMGB1 gene in women with recurrent pregnancy loss (though the timing during pregnancy is unspecified), further indirect evidence of enhanced T H 17 activity as this alarmin increases T H 17 activity (Jin et al, 2015).…”

Section: Recurrent Spontaneous Abortion (Rsa)mentioning

confidence: 97%

The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders

Osborne

Brar

Klein

2019

Brain, Behavior, and Immunity

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T cells play a key role in adaptive immune responses, and shifts among T cell classes occur in normal pregnancy. There is evidence for the role of T H 17 cells and dysregulation of the T H 17:T reg cell balance in morbidities and autoimmune diseases during pregnancy. Because T H 17 responses may play a role in depression and anxiety outside of pregnancy, we hypothesize that T H 17 responses and the balance of T H 17:T reg activity may also contribute to the development of depression and anxiety during pregnancy. To explore this hypothesis, this review has three main aims: 1) to evaluate systematically the role of T H 17 cells and cytokines during pregnancy; 2) to compare changes in the ratio of T H 17:T reg cells during pregnancy morbidities with the changes that occur in depression and anxiety outside of pregnancy; and 3) to provide a basis for further research on T H 17 cells in perinatal mood and anxiety disorders, with an eye toward the development of novel therapeutics. We also review the limited literature concerning perinatal mood and anxiety disorders, and hypothesize about the potential role of T H 17 cells in these illnesses. Understanding the pathophysiology of perinatal mood and anxiety disorders will aid development of novel therapeutics that address immunological mechanisms, in addition to the serotonin system, which are targetable molecules in treating depression and anxiety during pregnancy.

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“…Elevated HMGB1 levels in uterine fluids have been associated with pregnancy failure in rats and lower abundance of HMGB1 observed in the receptive phase of implantation in humans (Bhutada et al 2014). Additionally, a genetic polymorphism of HMGB1 characterized by higher expression of HMGB1 in placenta has been associated with RPL (Jin et al 2015). Furthermore, HMGB1 was shown to induce inflammation, characterized by an NF-κB-and reactive oxygen species-dependent increased secretion of IL-6, IL-8 and CCL2 in first-trimester trophoblast (Shirasuna et al 2016).…”

Section: Early Pregnancymentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

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Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.Reproduction (2016) 152 R277-R292

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High mobility group box 1 protein polymorphism affects susceptibility to recurrent pregnancy loss by up-regulating gene expression in chorionic villi

Abstract: These results suggest that HMGB1 rs2249825C/G polymorphism is associated with increased risk of RPL and can elevate gene expression in chorionic villi.

Cited by 18 publications

References 21 publications

Association of HMGB1 Gene Polymorphisms with Risk of Colorectal Cancer in a Chinese Population

Association of HMGB1 Gene Polymorphisms with Risk of Colorectal Cancer in a Chinese Population

The role of Th17 cells in the pathophysiology of pregnancy and perinatal mood and anxiety disorders

Sterile inflammation and pregnancy complications: a review

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