Association of the maternal 14‐bp insertion polymorphism in the HLA‐G gene in women with recurrent spontaneous abortions

Yan, Wei‐Hua; Lin, Aifen; Chen, X. J.; Dai, Meizhen; Gan, Lin-Hong; Zhou, Mengya; Zhu, Min; Shi, Wei-Wu; Liu, J. M.

doi:10.1111/j.1399-0039.2006.00723.x

Cited by 51 publications

(43 citation statements)

References 21 publications

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“…According to Yan et al (2006), a significantly different distribution of the 14-bp genotype exists among Chinese, Danish and Indian RM populations and the discrepancy may be a result of ethnic variation (see Table 3). When compared to these other ethnic groups, several trends, however, do persist.…”

Section: Discussionmentioning

confidence: 99%

Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran

Arjmand¹,

Samadi

2015

Journal of Immunotoxicology

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HLA-G is supposed to play a pivotal role in tolerance of the semi-allogeneic graft in pregnancy by inhibiting the cytotoxic functions of T and NK cells. A 14-bp insertion and/or deletion polymorphism in exon-8 has a possible role in HLA-G expression. The present study analyzed the 14-bp insertion/deletion polymorphism in normal pregnancy and recurrent miscarriage patients in order to discover a possible correlation between the 14-bp polymorphism and recurrent miscarriage (RM). In this study, genomic DNA from 200 RM patients and 200 normal fertile control individuals using the routine salting out method were isolated. Exon-8 of HLA-G gene of the two groups were amplified using polymerase chain reaction and analyzed by electrophoresis on 10% non-denaturing polyacrylamide gel electrophoresis containing ethidium bromide and visualized under ultraviolet light. HLA-G allele frequencies and genotypes in RM women and the fertile control group were compared using a Chi-square test. The results showed that there was a difference in allelic frequencies of 14-bp insertion polymorphism between fertile controls and RM patients; the frequency of +14 bp/À14 bp heterozygotes was significantly higher in RM patients as compared with fertile controls. Furthermore, the frequency of +14-bp insertion allele was significantly higher in those with RM as compared with normal fertile controls. From the findings here, it was concluded that a 14-bp insertion/deletion polymorphism in exon 8 could play a possible role in recurrent miscarriages. These results might ultimately be of significance for clinicians and those involved in understanding infertility and RM.

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Section: Discussionmentioning

confidence: 99%

Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran

Arjmand¹,

Samadi

2015

Journal of Immunotoxicology

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“…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%

“…Association between RM and HLA-G 14-bp insertion/deletion polymorphism allele Sixteen studies were included in assessing the association between HLA-G 14-bp insertion/deletion polymorphism allele and RM [12,17,[25][26][27][40][41][42][43][44][45][46][47][48][49][50]. As shown in Fig.…”

Section: Studies Included In the Meta-analysismentioning

confidence: 99%

“…A deletion/ insertion (DEL/INS) of 14 base pairs (14 bp) polymorphism at the 3′ UTR was clearly implicated [15]. The presence of the 14 bp INS affected mRNA stability, protein production [16] and was associated with pregnancy pathologies and autoimmune diseases [17], [18]. HLA-G allele containing 14-bp sequence was associated with a significantly lower mRNA levels than that containing the 14-bp sequence deleted [19][20][21] and related with a lower HLA-G protein production [15], [22].…”

Section: Introductionmentioning

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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“…Interestingly, a 100% presence of HLA-G*010401 was seen in the 11 abortion cases, while it was present in only 51.9% of the cases that were a success. [77] In 2006, a Chinese team could not find the association between HLA-G and RSA; [78,79] also, a Polish study failed to do so, [80] albeit the team suggested that nonsignificance was probably due to the small sample size. [81] Two other negative studies were published -one in 2010 that analyzed 143 RSA and 150 control couples in the Indian population [82] and another one in 2012 on an Iraqi population of 50 RSA and 50 control women.…”

Section: "Wrong" Hla Programmingmentioning

confidence: 99%

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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Association of the maternal 14‐bp insertion polymorphism in the HLA‐G gene in women with recurrent spontaneous abortions

Cited by 51 publications

References 21 publications

Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran

Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran

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

Genetic regulation of recurrent spontaneous abortion in humans

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