HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels

Hviid, Thomas Vauvert F.; Hylenius, Sine; Rørbye, Christina; Nielsen, Lene Nørby

doi:10.1007/s00251-003-0547-z

Cited by 327 publications

(266 citation statements)

References 68 publications

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“…The 3′-untranslated region (3′UTR) of the HLA-G gene also exhibits several regulatory elements including AU-rich motifs and a poly-A signal to influence mRNA stability, turnover, mobility, and splicing pattern (20, 28). Polymorphisms in these regions may thus affect the expression of HLA-G by altered regulation of gene transcription or by destabilizing the mRNA transcript (28–30).…”

Section: The Hla-g Genementioning

confidence: 99%

“…Polymorphisms in these regions may thus affect the expression of HLA-G by altered regulation of gene transcription or by destabilizing the mRNA transcript (28–30). Indeed, several important polymorphisms have been described in the 5′URR and the 3′UTR of the HLA-G gene (28, 29, 31–34). …”

Section: The Hla-g Genementioning

confidence: 99%

“…Since the 3′UTR of the HLA-G gene exhibits several regulatory elements including AU-rich motifs, a poly-A signal, as well as signals that regulate the spatial and temporal expression of mRNA, the polymorphic sites may influence mRNA stability, turnover, mobility, and splicing pattern (20, 28, 30). A 14-bp ins/del (rs66554220) located in exon 8 is the best studied polymorphism in the 3′UTR, and has been shown to influence HLA-G mRNA transcript size and stability (19, 28, 30, 31, 40–42). The presence of the 14-bp-insertion sequence introduces an alternative splice site that generates a 92-bp deletion in the 3′UTR of the HLA-G mRNAs, and this alternative splice form seems to have an impact on the expression levels of HLA-G (5, 28, 40, 41).…”

Section: The Hla-g Genementioning

confidence: 99%

“…A 14-bp ins/del (rs66554220) located in exon 8 is the best studied polymorphism in the 3′UTR, and has been shown to influence HLA-G mRNA transcript size and stability (19, 28, 30, 31, 40–42). The presence of the 14-bp-insertion sequence introduces an alternative splice site that generates a 92-bp deletion in the 3′UTR of the HLA-G mRNAs, and this alternative splice form seems to have an impact on the expression levels of HLA-G (5, 28, 40, 41). The positions of polymorphism in the 3′UTR of the HLA-G gene are in the current review numbered according to the publication by Castelli et al, which includes the 14-bp sequence in the reference sequence (43).…”

Section: The Hla-g Genementioning

confidence: 99%

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Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in Reproduction

2014

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In several years after its discovery in the placenta, the human leukocyte antigen (HLA) class Ib protein, HLA-G, was not given much attention, nor was it assigned great importance. As time has unraveled, HLA-G has proven to have distinctive functions and an unforeseen and possibly important role in reproduction. HLA-G is characterized mainly by its low polymorphism and restricted tissue distribution in non-pathological conditions. In fact, its expression pattern is primarily limited to extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. Due to low polymorphism, almost the same protein is expressed by virtually all individuals. It is these unique features that make HLA-G differ from its highly polymorphic HLA class Ia counterparts, the HLA-A, -B, and -C molecules. Its function, seemingly diverse, is typically receptor-mediated, and involves interactions with a wide range of immune cells. As the expression of HLA-G primarily is limited to gestation, this has given rise to the hypothesis that HLA-G plays an important role in the immunological tolerance of the fetus by the mother. In keeping with this, it might not be surprising that polymorphisms in the HLA-G gene, and levels of HLA-G expression, have been linked to reproductive failure and pre-eclampsia. Based on recent studies, we speculate that HLA-G might be involved in mechanisms in reproductive immunology even before conception because HLA-G can be detected in the genital tract and in the blood of non-pregnant women, and is present in seminal fluid from men. In addition, HLA-G expression has been found in the pre-implanted embryo. Therefore, we propose that a combined contribution from the mother, the father, and the embryo/fetus is likely to be important. Furthermore, this review presents important aspects of HLA-G in relation to reproduction: from genetics to physiological effects, from pregnancy and pregnancy complications to a short discussion on future possible means of preventative measures and therapy.

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Section: The Hla-g Genementioning

confidence: 99%

Section: The Hla-g Genementioning

confidence: 99%

Section: The Hla-g Genementioning

confidence: 99%

Section: The Hla-g Genementioning

confidence: 99%

See 2 more Smart Citations

Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in Reproduction

2014

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“…Amongst these 3’UTR polymorphisms (Figure 1), a 14-bp indel (rs66554220) has been the most studied and has been associated with the magnitude of HLA-G production, with modulation of HLA-G mRNA stability, and with binding for specific microRNAs (Castelli et al, 2014). In general, the presence of a 14-bp insertion ( Ins ) (5’-ATTTGTTCATGCCT-3’) introduces an alternative splicing site that generates a 92-bp deletion in the 3’UTR that influences mRNA stability; and individuals with Ins/Ins genotype have been associated with lower mRNA production compared to Ins/Del and Del/Del genotypes (Hviid et al, 2003, Castelli et al, 2010, Castelli et al, 2009). Furthermore, other 3’UTR SNPS have also been implicated in the regulation of HLA-G expression.…”

Section: Introductionmentioning

confidence: 99%

Maternal human leukocyte antigen-G (HLA-G) genetic variants associate with in utero mother-to-child transmission of HIV-1 in Black South Africans

Hong

Paximadis

Gray

et al. 2015

Infection, Genetics and Evolution

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A 14-bp insertion/deletion (indel) within the 3' untranslated region (3’UTR) that affects HLA-G expression has been associated with HIV-1 mother-to-child transmission (MTCT). However, other 3’UTR single nucleotide polymorphisms (SNPs) that influence HLA-G mRNA stability have been described but not analyzed in the context of MTCT, and little is known about the role of HLA-G alleles. We examined HLA-G alleles and 3’UTR SNPs, including the 14-bp indel, in 216 mother-infant pairs from Johannesburg, South Africa. Mother-infant pairs were classified as HIV-1 non-transmitting (NT, n=144) or HIV-1 transmitting (TR, n=72) with either intrapartum (IP, n=29) or in utero (IU, n=19) infected infants. We found HLA-G allele, G*01:01:02 (in strong linkage disequilibrium with the 14-bp insertion) and +3187G SNP were significantly over-represented in IU-TR mothers compared to NT mothers (P=0.036, OR=2.26; P=0.011, OR=2.96, respectively). These findings suggest that maternal HLA-G alleles and/or SNPs that might alter expression of HLA-G potentially influence IU HIV-1 MTCT.

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Human leukocyte antigen‐G polymorphisms influence the clinical outcome in diffuse large B‐cell lymphoma

Bielska

Bojo

Klimkiewicz-Wojciechowska

et al. 2015

Genes Chromosomes & Cancer

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The role of HLA-G is extensively studied in cancer due to its inhibition of the immune response. Several polymorphisms in the HLA-G gene have been reported to significantly affect its expression. We, therefore, investigated whether functionally relevant HLA-G polymorphisms, HLA-G-725C/G/T, and HLA-G 14-base pair, have any influence on the susceptibility to diffuse large B-cell lymphoma (DLBCL) and its clinical course. The polymorphisms were genotyped in 207 previously untreated patients with DLBCL and 150 unrelated controls. A significant difference in genotype distribution of HLA-G polymorphic genotypes between the patients and controls was found. The frequencies of the HLA-G-725GG or the HLA-G-725GC genotype were lower, and those of the HLA-G ins/ins genotype were higher in the patients compared with the controls. Patients carrying the HLA-G-725CC genotype presented a higher probability of overall survival (OS) than subjects with other genotype combinations of HLA-G-725C/G/T (P = 0.003). The homozygous HLA-G del/del had a lower probability of OS than subjects carrying the HLA-G deletion/insertion (del/ins) or the HLA-G ins/ins genotype (P = 0.009). Two HLA-G genotype-based risk groups were defined according to the genotype distribution. The high-risk (HR) group presented a shorter OS than low-risk (LR) patients (P = 0.001). In a multivariate analysis adjusted for International Prognostic Index (IPI) factors, both the intermediate high/high IPI-risk group (P < 0.0001) and the HR genotype group (P = 0.004) independently increased the risk of death. This is the first study indicating an important role of HLA-G polymorphisms for the clinical course of DLBCL. The potential influence of HLA-G polymorphisms on the susceptibilityto DLBCL thus deserves further study.

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HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels

Cited by 327 publications

References 68 publications

Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in Reproduction

Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in Reproduction

Maternal human leukocyte antigen-G (HLA-G) genetic variants associate with in utero mother-to-child transmission of HIV-1 in Black South Africans

Human leukocyte antigen‐G polymorphisms influence the clinical outcome in diffuse large B‐cell lymphoma

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