Polymorphism in killer cell immunoglobulin-like receptors and human leukocyte antigen-c and predisposition to preeclampsia in Ethiopian pregnant women population

Kelemu, Tsehayneh; Erlandsson, Lena; Seifu, Daniel; Hansson, Eva Ekvall; Abebe, Markos; Teklu, Sisay; Girma, Selfu; Traherne, James A.; Moffett, Ashley; Hansson, Stefan R.

doi:10.1016/j.jri.2020.103169

Cited by 15 publications

(15 citation statements)

References 33 publications

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“…However, our results suggest that low levels of maternal CD99 are only important when the embryo is male. Our recent study showed an association between PE and a maternal killer cell immunoglobulin-like receptor (KIR) inhibitory genotype expressed in the uNK cells, demonstrating the important role played by uNK cells in pregnancy outcome [49]. However, there was no association between the maternal rs311103 genotype frequencies described in this study and the maternal KIR genotypes previously described.…”

Section: Discussioncontrasting

confidence: 70%

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Association of Maternal Regulatory Single Nucleotide Polymorphic CD99 Genotype with Preeclampsia in Pregnancies Carrying Male Fetuses in Ethiopian Women

Kelemu

Erlandsson

Seifu

et al. 2020

IJMS

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Preeclampsia (PE) is a human specific syndrome with unknown etiology causing maternal and fetal morbidities and mortalities. In PE, maternal inflammatory responses are more exaggerated if the fetus is male than female. Other pregnancy complications such as spontaneous abortions are also more common if the fetus is male. Recent transcriptome findings showed an increased expression of CD99 in erythroid cells from male cord blood in PE. The single nucleotide polymorphism (SNP) rs311103, located in a GATA-binding site in a regulatory region on the X/Y chromosomes, governs a coordinated expression of the Xg blood group members CD99 and Xga in hematopoietic cells in a sex-dependent fashion. The rs311103C disrupts the GATA-binding site, resulting in decreased CD99 expression. We aimed to investigate the association between PE and the allele frequency of rs311103 in pregnancies in a fetal sex-dependent fashion. In a case-controlled study, we included 241 pregnant women, i.e., 105 PE cases and 136 normotensive controls. A SNP allelic discrimination analysis was performed on DNA from maternal venous blood and fetal cord blood by qPCR. A statistically significant association was observed between rs311103 allele frequency and PE in mothers carrying male fetuses. Therefore, the rs311103 genotype may play a role in the pathogenesis of PE in a fetal sex-specific manner.

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Section: Discussioncontrasting

confidence: 70%

“…The participants were recruited based on the order of their visit to the Obstetrics and Gynecology delivery ward. The cohort has been used in a previous study [49].…”

Section: Study Design and Study Participantsmentioning

confidence: 99%

Association of Maternal Regulatory Single Nucleotide Polymorphic CD99 Genotype with Preeclampsia in Pregnancies Carrying Male Fetuses in Ethiopian Women

Kelemu

Erlandsson

Seifu

et al. 2020

IJMS

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“…The importance of contextualizing programs, interventions, and technologies was highlighted in publications that provided contributions and insights regarding the development of an evidence-based answer to the third foundational research question. Variations in genotypes among population groups, for example, can have significant implications for treatment in areas such as breast cancer (Hadgu et al, 2020 ) and preeclampsia (Kelemu et al, 2020a , 2020b ). Important differences also exist in the prevalence of chronic kidney disease (CKD; Molla et al, 2020 ), abnormal glucose tolerance (Hobabagabo et al, 2020 ), and in-hospital mortality rates for older adults (Orikiriza et al, 2020 ).…”

Section: Foundational Research Questionsmentioning

confidence: 99%

“…Characteristics of individuals: Self-efficacy What interventions and technologies are key to eradicating global health inequities? •Interventions and devices must fit local contexts •Appropriate funding is essential •Barriers to service provision must be understood •Public messaging with ongoing evaluative research can maximise behaviour change Hadgu et al ( 2020 ), Kelemu et al ( 2020a , 2020b ), Molla et al ( 2020 ), Hobabagabo et al ( 2020 ), Orikiriza et al ( 2020 ), Chandler et al ( 2020 ), Carey and Gullifer ( 2020a ), *Leckning et al ( 2020 ), Carey et al ( 2020a , 2020b ), Iverson et al 2020 ), HIrschhorn et al ( 2020 ), Wotton and Binagwaho ( 2020 ), Isano et al ( 2020 ), Louis et al ( 2020 ), Lazarus et al ( 2020b ), Ratzan et al ( 2020 ), *Nduwayezu et al ( 2020 ), Harrington et al ( 2020 ), Forrester et al ( 2020 ), Atun et al ( 2020 ), Semret et al ( 2020 ), *Ndayambaje et al ( 2020 ), Chu et al ( 2020 ), Kediso et al ( 2020 ), Tuasha et al ( 2020 ), Owolabi et al ( 2020a , 2020b ), Karangwa et al ( 2020 ), Carey and Gullifer ( 2020b ), Landrigan et al ( 2020 ), Binagwaho et al ( 2020 ) I. Intervention characteristics: Adaptability; complexity; cost II.…”

Section: Introductionmentioning

confidence: 99%

Solving the Puzzle of Global Health Inequity: Completing the Picture Piece by Piece by Piece

Carey

2021

Glob Implement Res Appl

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Achieving health equity is an ongoing priority for the global community. Understanding, supporting, and addressing the challenges that face health workers is a critical component of the solution to this problem. The University of Global Health Equity (UGHE) in Rwanda has established the Institute of Global Health Equity Research (IGHER) to contribute to the generation of new knowledge through high-quality research and research training that seeks to improve our understanding of the important issues that influence the distribution of health and healthcare globally. With an unrelenting emphasis on increased impact by prioritizing implementation research, IGHER is particularly interested in amassing a compendium of important research lessons to increase the likelihood that effective implementation strategies will be employed to enhance healthcare service provision. IGHER organizes research according to five foundational research questions, which address different elements that are pivotal to a comprehensive approach to appreciating the nuanced realities of effective healthcare service provision. UGHE outputs for 2020 indicate that: appropriate resourcing of healthcare services is critical for the eradication of global health inequities; policy reform is required for many healthcare innovations and initiatives to be implemented adequately; and high-quality research that is applicable to different contexts is essential for eradicating global health inequities. Furthermore, reimagining healthcare delivery will benefit from an intentional, ongoing, bidirectional influence between evidence-based pedagogy (methods and practices of teaching, education, and instruction) and supporting research activity such that education and instruction inform the research conducted and research findings are fed back to the classroom to help improve education and instruction. As IGHER continues to grow, the valuable insights afforded by high-impact implementation research will increase. These insights will help to inform the development and use of evidence-based implementation strategies for the adoption, scaling, and sustainability of equitable, effective, and efficient health services globally.

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“…Since the invasion ability of the trophoblast is affected, inappropriate combinations of KIR/HLA-C are reasons that cause PE. Reportedly, if a woman carries the KIR AA genotype and her baby has HLA-C2 from the father, then the possibility of PE in the pregnancy was increased ( 20 , 76 ) ( Table II ). This is because KIR AA/HLA-C2 binding may lead to inadequate activation of uNK cells, affecting uterine artery recasting and leading to PE.…”

Section: Kir/hla-c Combination and Gosmentioning

confidence: 99%

Killer‑cell immunoglobulin‑like receptor/human leukocyte antigen‑C combination and ‘great obstetrical syndromes’ (Review)

Yang

Meng

2021

Exp Ther Med

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Recurrent pregnancy loss (RPL), pre-eclampsia (PE), fetal growth restriction (FGR), and preterm delivery are examples of 'great obstetrical syndromes' (GOS). Placental dysfunction is the most common pathogenesis of GOS. In human pregnancies, the effects of uterine natural killer cells involve angiogenesis, promoting the remodeling of uterine spiral artery, and improving the invasion of trophoblast cells. The uNK cells supply killer immunoglobulin-like receptors (KIRs), which come into contact with human leukocyte antigen-C (HLA-C) ligands expressed by extravillous trophoblast cells (EVTs). Numerous studies have investigated the association between GOS and KIR/HLA-C combination. However, the outcomes have not been conclusive. The present review aimed to reveal the association between GOS and KIR/HLA-C combination to screen out high-risk pregnancies, strengthen the treatment of pregnancy complications, and reduce the frequency of adverse maternal and fetal outcomes. It has been reported that a female with a KIR AA genotype and a neonate with a paternal HLA-C2 molecule is more prone to develop GOS and have a small fetus since less cytokines were secreted by uNK cells. Conversely, the combination of KIR BB haplotype (including the activating KIR2DS1) and HLA-C2 can induce the production of cytokines and increase trophoblast invasion, leading to the birth of a large fetus. KIR/HLA-C combinations may be applicable in selecting third-party gametes or surrogates. Detection of maternal KIR genes and HLA-C molecules from the couple could serve as useful markers for predicting and diagnosing GOS.

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Polymorphism in killer cell immunoglobulin-like receptors and human leukocyte antigen-c and predisposition to preeclampsia in Ethiopian pregnant women population

Cited by 15 publications

References 33 publications

Association of Maternal Regulatory Single Nucleotide Polymorphic CD99 Genotype with Preeclampsia in Pregnancies Carrying Male Fetuses in Ethiopian Women

Association of Maternal Regulatory Single Nucleotide Polymorphic CD99 Genotype with Preeclampsia in Pregnancies Carrying Male Fetuses in Ethiopian Women

Solving the Puzzle of Global Health Inequity: Completing the Picture Piece by Piece by Piece

Killer‑cell immunoglobulin‑like receptor/human leukocyte antigen‑C combination and ‘great obstetrical syndromes’ (Review)

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