<scp>HLA</scp>‐G regulatory variants and haplotypes with susceptibility to recurrent pregnancy loss

Yazdani, Neda; Khaniani, Mahmoud Shekari; Bastami, Milad; Ghasemnejad, Tohid; Afkhami, Fatemeh; Derakhshan, Sima Mansoori

doi:10.1111/iji.12364

Cited by 17 publications

(12 citation statements)

References 33 publications

(61 reference statements)

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“…In 2014, yet another meta-analysis indicated that there was only an association between the HLA-G 14-bp indel polymorphism and RM in patients with three or more miscarriages [27]. In the present study, we have not addressed polymorphisms in the HLA-G promotor region, but they may be associated to RM, as recently shown [28].…”

Section: Discussionmentioning

confidence: 80%

Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels

Craenmehr

Nederlof

Cao

et al. 2019

IJMS

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Human leukocyte antigen (HLA)-G is an immune modulating molecule that is present on fetal extravillous trophoblasts at the fetal-maternal interface. Single nucleotide polymorphisms (SNPs) in the 3 prime untranslated region (3′UTR) of the HLA-G gene can affect the level of HLA-G expression, which may be altered in women with recurrent miscarriages (RM). This case-control study included 23 women with a medical history of three or more consecutive miscarriages who delivered a child after uncomplicated pregnancy, and 46 controls with uncomplicated pregnancy. Genomic DNA was isolated to sequence the 3′UTR of HLA-G. Tissue from term placentas was processed to quantify the HLA-G protein and mRNA levels. The women with a history of RM had a lower frequency of the HLA-G 3′UTR 14-bp del/del genotype as compared to controls (Odds ratio (OR) 0.28; p = 0.039), which has previously been related to higher soluble HLA-G levels. Yet, HLA-G protein (OR 6.67; p = 0.006) and mRNA (OR 6.33; p = 0.010) expression was increased in term placentas of women with a history of RM as compared to controls. In conclusion, during a successful pregnancy, HLA-G expression is elevated in term placentas from women with a history of RM as compared to controls, despite a genetic predisposition that is associated with decreased HLA-G levels. These findings suggest that HLA-G upregulation could be a compensatory mechanism in the occurrence of RM to achieve an ongoing pregnancy.

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Section: Discussionmentioning

confidence: 80%

Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels

Craenmehr

Nederlof

Cao

et al. 2019

IJMS

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“…Also, SNP mutations in the HLA-G promoter region are important from the point of view of maintaining pregnancy. Research in this field was conducted by Yazdani et al [33], who investigated the –1573T> C and –1746C> A SNP mutations in the HLA-G promoter region, associated with recurrent spontaneous abortion. Their haplotype analysis revealed a significant link between recurrent miscarriages and the H1 (ATCCAGGTACGCAA) and H2 (CTTCGAGAACGCAG) haplotypes.…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of HLA-G in Women with High-Risk Pregnancy and Their Partners with Regard to Possible Complications

Sipak

Rył

Grzywacz

et al. 2019

IJERPH

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The understanding of the molecular and biochemical characteristics of the human leukocyte antigen-G (HLA-G) is important because of the diverse influence of this antigen’s polymorphisms on the course of a pregnancy. The aim of our study was to assess how the variation of the HLA-G allele and the HLA-G 14-bp ins/del polymorphism influence predisposition to a complicated pregnancy. The clinical material consisted of parental pairs with complicated pregnancies (210 women; 190 men). The control group included parental pairs without complications during pregnancy (89 women; 86 men). The study involved isolation of genome DNA from peripheral blood leukocytes, sequencing, and analysis of the 14-bp ins/del polymorphism in the 3′-untranslated region (3′-UTR) of the HLA-G gene based on polymerase chain reaction (PCR). The most common HLA-G allele in the group of women with complicated pregnancies was the HLA-G 10101 allele. There were no statistically significant differences in the frequencies of the 14-bp ins/del polymorphism in the 3′UTR of the HLA-G gene between the groups. Our results suggest that the risk of complications in pregnancy is influenced by the HLA-G 10101, HLA-G 10108, and HLA-G 10106 alleles and is not influenced by the 14-bp ins/del polymorphism in the 3′UTR of the HLA-G gene.

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“…Also, a study has reported that decreased expression of HLA-G suppresses the function of decidual NK cells and thereby may lead to RSA [28]. SNPs−1573T>C and −1746C>A in the promoter region of HLA-G gene are shown to be associated with RSA [29]. As the level of sHLA-G is known to be associated with the pregnancy complication, the measurement of sHLA-G protein may be useful in primary diagnosis for the pathogenesis of pregnancy complications.…”

Section: Hla-g and Pregnancy Disordersmentioning

confidence: 99%

Alloimmunization and Role of HLA in Pregnancy

Singh¹,

Rajak²,

Rajadhyaksha³

2019

Complications of Pregnancy

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Alloimmunization also known as isoimmunization, during pregnancy is the production of IgG antibodies by the mother against the paternally inherited antigens (IPA) in the foetus/newborn. The alloimmunization during pregnancy leads to various alloimmune disorders, such as, haemolytic disease of the foetus and newborn (HDFN), neonatal alloimmune neutropenia (NAN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT) due to the production of maternal alloantibodies against the red blood cell antigen, neutrophils and platelets cell antigens, respectively. Recent studies suggest that maternal anti-HLA class I alloantibodies may also be the cause of FNAIT in addition to antibodies against platelet antigens. On the contrary, studies have also suggested that HLA-C, a classical HLA class I molecule, and HLA-G, a nonclassical HLA molecule, play an important role in placentation and modulation of the maternal immune system during pregnancy, respectively, and thereby leading to acceptance of the semi allogeneic fetus. So far most of the studies have discussed alloimmunization in pregnancy relating to Rh antigen. Thus, in this chapter an attempt has been made to discuss alloimmunization in pregnancy caused because of maternal alloantibody against HLA antigen and its role in immune modulation during pregnancy.

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HLA‐G regulatory variants and haplotypes with susceptibility to recurrent pregnancy loss

Cited by 17 publications

References 33 publications

Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels

Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels

Molecular Analysis of HLA-G in Women with High-Risk Pregnancy and Their Partners with Regard to Possible Complications

Alloimmunization and Role of HLA in Pregnancy

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