Is <scp>HLA</scp><i>‐</i>E a possible genetic marker relevant for natural conception?

Gelmini, Georgia Fernanda; Costa, Cynthia Hernandes; Nardi, Fabiola da Silva; Wowk, Pryscilla Fanini; Mattar, S. B.; Schuffner, Alessandro; Bicalho, Maria da Graça; Roxo, Valéria Maria Munhoz Sperandio

doi:10.1111/aji.12587

Cited by 5 publications

(10 citation statements)

References 25 publications

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“…The GO enrichment analysis for the DMRs indicated that the genes were mainly enriched in the GO terms, including HES4, PRKCZ,SKI,PRDM16,ALPL,RUNX3,TAL1,TTLL7,BARHL2,OLFM3,NFYC,TBX15,LMX1A,TNFRSF4,AJAP1,SYTL1,OPRD1,PTPRU,PRRX1,ELF3,PROX1, (Table 4). Among these, we screened HLA-G (P = 1.86E−30), HLA-E (P = 9.42E−11), and PRDM16 (P = 1.86E−30), which are closely related to embryonic development, as candidate genes of RM (Gelmini et al, 2016;Horn et al, 2011;Verloes et al, 2017).…”

Section: Go Enrichment Analysis and Go-tree Of The Dmrsmentioning

confidence: 99%

DNA methylation profiling in recurrent miscarriage

Zhang

et al. 2020

PeerJ

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Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RM-related biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1,799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM–receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

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Section: Go Enrichment Analysis and Go-tree Of The Dmrsmentioning

confidence: 99%

DNA methylation profiling in recurrent miscarriage

Zhang

et al. 2020

PeerJ

View full text Add to dashboard Cite

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“…The GO enrichment analysis for the DMRs indicated that the genes were mainly enriched in the GO terms, including HES4, PRKCZ,SKI,PRDM16,ALPL,RUNX3,TAL1,TTLL7,BARHL2,OLFM3,NFYC,TBX15,LMX1A,TNFRSF4,AJAP1,SYTL1,OPRD1,PTPRU,PRRX1,ELF3,PROX1, HLA-G, and HLA-E (Table 4). Among these, we screened HLA-G (P=1.86E-30), HLA-E (P=9.42E-11), and PRDM16 (P=1.86E-30), which are closely related to embryonic development, as candidate genes of RM (Gelmini et al 2016;Horn et al 2011;Verloes et al 2017).…”

Section: Go Enrichment Analysis and Go-tree Of The Dmrsmentioning

confidence: 99%

“…Among these, we screened ALCAM (P=3.00E-08), HLA-G (P=3.00E-08), and HLA-E (P=3.00E-08), which are closely related to embryonic development, as candidate genes of RM (Cizelsky & Tata 2014;Gelmini et al 2016;Verloes et al 2017).…”

Section: Pathway Enrichment Analysis Of the Dmrsmentioning

confidence: 99%

“…Besides its immunosuppressive function in transplantation, HLA-G expression is involved in implantation and protection of the semi-allogeneic fetus from the maternal immune system (Carosella et al 2008;Hunt et al 2005;Rebmann et al 2007). Studies have proposed that HLA-G plays an important role in early embryonic development (Yao et al 2014 Manuscript to be reviewed leukocyte antigens) act in the immunology of human reproduction as modulators of the maternal immune system during pregnancy (Gelmini et al 2016). Recent studies have shown the functions of the HLA-E molecule and possible interactions with HLA-G.…”

Section: Mrna Relative Expression Level Of the Candidate Genes In 24 mentioning

confidence: 99%

“…Recent studies have shown the functions of the HLA-E molecule and possible interactions with HLA-G. The relevance of HLA-G and HLA-E expression in the maternal-fetal interface seems to be regarding the inhibition of NK cellmediated lysis and possible influence on cytokine profiles (Gelmini et al 2016). Pregnancy is a condition where women undergo major physiological and immunological alterations (Mishra et al 2019), which are likely to be influenced or controlled by abnormal methylation levels of HLA-G and HLA-E.…”

Section: Mrna Relative Expression Level Of the Candidate Genes In 24 mentioning

confidence: 99%

See 2 more Smart Citations

Peer Review #1 of "DNA methylation profiling in recurrent miscarriage (v0.1)"

2020

View full text Add to dashboard Cite

Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RMrelated biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM-receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

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HLA class Ib in pregnancy and pregnancy-related disorders

et al. 2017

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The HLA class Ib genes, HLA-E, HLA-F, and HLA-G, were discovered long after the classical HLA class Ia genes. The elucidation of their functions had a modest beginning. However, their basic functions and involvement in pathophysiology and a range of diseases are now emerging. Although results from a range of studies support the functional roles for the HLA class Ib molecules in adult life, especially HLA-G and HLA-F have most intensively been, and were also primarily, studied in relation to reproduction and pregnancy. The expression of HLA class Ib proteins at the feto-maternal interface in the placenta seems to be important for the maternal acceptance of the semi-allogenic fetus. In contrast to the functions of HLA class Ia, HLA-G possesses immune-modulatory and tolerogenic functions. Here, we review an accumulating amount of data describing the functions of HLA class Ib molecules in relation to fertility, reproduction, and pregnancy, and a possible role for these molecules in certain pregnancy complications, such as implantation failure, recurrent spontaneous abortions, and pre-eclampsia. The results from different kinds of studies point toward a role for HLA class Ib, especially HLA-G, throughout the reproductive cycle from conception to the birth weight of the child.

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Is HLA‐E a possible genetic marker relevant for natural conception?

Abstract: These results suggest that HLA-E allelic variants may play a role in the modulation of immune responses in the context of the inability of natural conception and establishment of a viable pregnancy.

Cited by 5 publications

References 25 publications

DNA methylation profiling in recurrent miscarriage

DNA methylation profiling in recurrent miscarriage

Peer Review #1 of "DNA methylation profiling in recurrent miscarriage (v0.1)"

HLA class Ib in pregnancy and pregnancy-related disorders

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