Association of HLA-G alleles and 3′ UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples

Vargas, Rafael Gustavo; Sarturi, Paulo Roberto; Mattar, S. B.; Bompeixe, Eni Picchioni; Silva, Joandrei dos Santos; Pirri, Alessandro; Bicalho, Maria da Graça

doi:10.1016/j.humimm.2011.02.011

Cited by 36 publications

(30 citation statements)

References 64 publications

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“…Twelve SNPs differed between the two groups of patients, while the authors also confirmed the increased risk brought by the 14-bp insertion. [88] This concurred with the results of two Brazilian studies, the first one analyzing 60 RSA couples and 60 controls [89] and the second one analyzing the outcome of IVF procedures which found an increase dfrequency of allele HLA-G*01:03:01 in the cases of implantation failures. This story was interestingly refined in 2012, with the idea of a sex-dependent increased risk, when the mother was + 14 bp/+14 bp homozygote and presented with HLA Class II alleles restricting HY immunity.…”

Section: "Wrong" Hla Programmingsupporting

confidence: 80%

Genetic regulation of recurrent spontaneous abortion in humans

Vaiman¹

2015

Biomed J

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Recurrent pregnancy loss, defined as a pregnancy failure occurring before 24 weeks of gestation more than two or three times according to most definitions, is a fertility defect encountered in 1-5% of the patients. This defect is of course of multifactorial origin. Among the possible origins of recurrent pregnancy loss are uterine structural defaults, defective ploidy control of the embryo, defective immunological dialog between the embryo (or the fetus) and the uterus sometimes in relation with immunological disorders (such as autoimmune diseases), thrombophilia, and free radical metabolism imbalance. Numerous studies attempted to correlate variants of genes supposed to be intervening in the different facets of the early maternal-fetal or maternal-embryonic dialog, and eventually modify the outcome of fertilization, leading to success or failure of post-implantation development. The objective of the present review is to portray the major genes and gene polymorphisms studied for their putative association with recurrent pregnancy loss. Most of these genes have been studied as candidate genes for which strong biological arguments were put forward as to their putative involvement in recurrent pregnancy loss. They were mostly studied by genetic analysis, often in various populations of different ethnic origins, throughout the world. Some of these studies were available only in English as abstracts and were nevertheless used if the information was given with enough detail. With the space being too short to depict all the available literature, different major pathways releva nt to the scientific question are presented without any attempt to hide the fact that discordant views often aroused for a given gene. rather attempt to categorize the factors that were analyzed according to their biological functions and summarize their putative effects.

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Section: "Wrong" Hla Programmingsupporting

confidence: 80%

Genetic regulation of recurrent spontaneous abortion in humans

Vaiman¹

2015

Biomed J

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“…The overall lack of association between the polymorphisms and RM might be due to some other unidentified functional mutations that existed in the HLA-G gene, affecting the susceptibility to RM. It was suggested that HLA-G*01:04:01 showed a negative association with the 14 bp segment in RM patients and a positive association in controls [42], and the T allele of HLA-G T1570C was in linkage disequilibrium with the 14-bp deletion in cases of RM [46]. Therefore, the association between the HLA-G 14-bp insertion/deletion polymorphism and RM may be influenced by other loci.…”

Section: Discussionmentioning

confidence: 99%

“…Among these, 4 studies were excluded due to duplicate publications [32][33][34][35], three had incomplete data on allele and genotype frequency which we failed to get by emails to the corresponding authors [36][37][38], and an additional one was excluded due to the absence of a control group [39]. Consequently, the remaining 17 case-control studies which examined the association between the HLA-G 14-bp polymorphism and RM were finally included [12,17,[25][26][27][40][41][42][43][44][45][46][47][48][49][50][51] (Fig. 1).…”

Section: Studies Included In the Meta-analysismentioning

confidence: 99%

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Relationship between HLA-G polymorphism and susceptibility to recurrent miscarriage: A meta-analysis of non-family-based studies

Fan

Huang

et al. 2013

J Assist Reprod Genet

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Purpose The HLA-G 14-bp insertion/deletion polymorphism had been inconsistently associated with recurrent miscarriage (RM) risk. We examined the association by performing a meta-analysis. Methods Eligible articles were searched in PubMed, EMBASE and CNKI without language limitation. We included all the articles about two or more miscarriages associated with HLA-G 14-bp polymorphism. The odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA10.0 software. Results 17 studies were included, representing 1786 cases and 1574 controls. The current meta-analysis showed that 14-bp polymorphism was not associated with RM risk in all genetic models and allele contrast(+14 bp vs. −14 bp: OR=1.13; 95 % CI, 0.96,1.32; +14 bp/+14 bp vs. −14 bp/−14 bp: OR=1.16, 95 % CI, 0.85, 1.59; +14 bp/−14 bp vs. −14 bp/−14 bp: OR= 1.21, 95 % CI, 0.92,1.58; dominant model: OR=1.33; 95 % CI, 0.99,1.78; recessive model: OR = 1.06; 95 % CI, 0.79,1.43). Moreover, a significant heterogeneity was evident across studies. On the other hand, the subgroup analysis demonstrated that there was a significant association between HLA-G 14-bp polymorphism and patients with three or more miscarriages(+14 bp vs. −14 bp: OR=1.27; 95 % CI, 1.04, 1.55; dominant model: OR=1.52; 95 % CI, 1.16, 1.99; and model +14 bp/−14 bp versus −14 bp/−14 bp: OR=1.51; 95 % CI, 1.15, 1.97;). Conclusions Our comprehensive meta-analysis indicated that there was insufficient evidence to demonstrate a conclusive association between the HLA-G 14-bp insertion/deletion polymorphism and the risk of RM. But HLA-G 14-bp insertion/ deletion polymorphic variation was associated with RM risk in patients with three or more miscarriages. Larger and welldesigned studies may eventually provide a better, comprehensive understanding of the association between the HLA-G 14-bp insertion/deletion polymorphism and RM in the future.

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“…In India, the alleles with the 14 bp insertion were also more frequent in patients with RPL compared to controls [101]. Vargas et al [102] found significantly elevated frequencies of recurrent miscarriages (RM) in Brasilian women with haplotype HLA-G*01:01:08/+14bp and HLA-G*01:04:01/-14bp. By contrast, the haplotype group HLA-G*01:01x/+14bp exhibited a significant protective effect against RPL occurrence.…”

Section: Hla-g and Pregnancy Disorders (Recurrent Pregnancy Loss Prementioning

confidence: 99%

Role of HLA-G and other immune mechanisms in pregnancy

et al. 2013

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Pregnancy loss (abortion) and pre-eclampsia represent the most common disorders in pregnant women. Besides infection, there are anatomical, endocrinological, genetic and immunological factors that can induce pregnancy disorders. Because the exact mechanisms of physiological pregnancy maintenance are still not clearly understood, the search for genes and proteins fulfilling this role is still in progress. One of the immune molecules that plays a beneficial role in pregnancy is the nonclassical HLA-G molecule. The molecule is mainly expressed on trophoblast cells in the foetal placenta and induces the immune tolerance of the foetus via its interaction with inhibitory receptors on maternal NK cells and CD8+ T lymphocytes. In relation to pregnancy disorders, associations between HLA-G polymorphism, HLA-G level and HLA-G function were described. Thus, the HLA-G molecule can be used as a new diagnostic marker and, potentially, for the future therapy of pregnancy disorders.

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Association of HLA-G alleles and 3′ UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples

Cited by 36 publications

References 64 publications

Genetic regulation of recurrent spontaneous abortion in humans

Genetic regulation of recurrent spontaneous abortion in humans

Relationship between HLA-G polymorphism and susceptibility to recurrent miscarriage: A meta-analysis of non-family-based studies

Role of HLA-G and other immune mechanisms in pregnancy

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