Association of HLA-G alleles and 3′ UTR 14 bp haplotypes with recurrent miscarriage in Brazilian couples (original) (raw)
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HLA-G displays immunotolerant properties and hence plays important roles in the maintenance of a successful pregnancy and maternal tolerance of the semiallogeneic fetus. HLA-G gene Polymorphism may potentially affect the biological properties of the protein, and a 14-bp insertion/deletion polymorphism in exon 8 of the 3 untranslated region (3 UTR) of the HLA-G gene is thought to influence HLA-G expression. To study the association of the 14-bp insertion/deletion (INDEL) polymorphism with the risk of recurrent pregnancy loss (RPL), polymerase chain reaction (PCR) amplification and genotyping were enrolled on 100 women in the case group (women who have had three or more unexplained RPL) and 100 women in the control group (women who have had at least two normal pregnancy). Our results showed that the frequencies of the+14 bp/+14 bp genotypes were not observed in women with RPL, while that of the +14 bp/?14 and -14 bp/-14 bp genotype was significantly increased in RPL compared with the control group of normal fertile women, in addition a significant differences in the allele frequencies of the HLA-G 14-bp polymorphism were observed. These results suggest a possible significance of the HLA-G 14-bp INDEL polymorphism in the outcome of pregnancy. However, further studies on other polymorphic sites in the 3 UTR and 5 UTR regions, as well as monitoring the serum HLA-G concentration are necessary in order to determine the potential implications of this marker in our population.
Role of 14-Bp HLA-G, INDEL Polymorphism in Recurrent Miscarriage
Global Journal of Health Science, 2016
Mothers and their fetuses are hereditarily unlike. Surprisingly, no less than 50% human pregnancies reach full term despite the tendency of the immune system to eliminate of non-self units. Reduction of adaptive maternal immune answer, which is planned to reject strange factors, is essential for a pregnancy to reach full term. However, approximately 5% couples trying to conceive experience 2 recurrent miscarriages (RMs). HLA-G, which is produced by the external trophectoderm layer and has unique biological features, is involved in the implantation and maintenance of fetus. Serum HLA-G levels are correlated with the risk of RM. Recent studies indicate that a 14-bp HLA-G, INDEL polymorphism decreases the level of HLA-G mRNA, which in turn decreases the amount of HLA-G produced. An understanding of gene parameter and the function of polymorphic sites in the functioning of HLA-G products may enable the development of approaches targeting HLA-G for more detail of causes of RM.
GENETIC POLYMORPHISMS OF HLA-G ANTIGEN IN IRAQI WOMEN WITH UNEXPLAINED RECURRENT MISCARRIAGE
This study was designed to search for HLA-G polymorphisms and its relationships with unexplained recurrent spontaneous abortion (URSA) among Iraqi women. In this study 300 aborted women have been chosen and they had history of recurrent spontaneous abortion as case group; in all cases full history and complete examinations including body weight, height and body mass index were done. Furthermore, all of the patients were screened for various known causes of miscarriages, including Anticardiolipin antibodies (IgM) , antiphospholipid (IgM), Coagulation factors including protein C, protein S, Antithrombin III, activated protein C resistance(APCR), and investigation of toxoplasmosis antibodies (IgM) and cytomegalovirus antibody (IgM), rubella antibody (IgM), as well homocysteine level , TSH and progesterone hormones. Based on the results of the screening test 33.6 % of cases are of unknown cause, So out of 300, only 100 case were enrolled in this study to investigate the association between RSA and three HLA-G alleles ( HLA-G*0103, HLA-G*0104 and HLA-G*0105N) and 14-bp insertion/deletion polymorphism in exon 8 of the 3untranslated region (3 UTR)frequency and genotypes in idiopathic RSA in Iraqi women compared with 100 control women without previous history of RSA, with at least two successful pregnancies In addition, the ELISA was conducted to investigate HLA-G serum levels in women with URSA and healthy women. The frequency of the allele and genotypes in the patient group and control group was determined using PCR-restriction fragment length polymorphism (PCR-RFLEP). Exon 3 of HLA-G gene amplified using specific primers then digested by PpuM-I and BseR-I restriction enzymes, in order to detect HLA-G*0105N and HLA-G*0104 alleles respectively. While exon 2 of HLA-G gene amplified using specific primers then digested with HinfI restriction enzyme to detect HLA-G*0103 allele. Genotypes for the mentioned alleles determined and tested for their association with URSA patients. Results of HLA-G allele frequency showed significant association with increased risk of URSA patients. HLA-G*0105N and HLA-G*0104 allele was present in URSA patients and fertile controls. HLA-G*0105N allele was found in 48.7% of the patient group while, it was present in 51.3% of the control group, odds ratio was 11.5759. HLA-G*0104 allele was present with high significant frequency of 71.3% in the patient group and 28.7% in the controls, odds ratio was 4.8947. While HLA-G*0103 allele was not encountered neither in the patient group nor in the control group. Aforementioned alleles genotyped, and two genotypes were encountered in both URSA patients and fertile control groups (HLA-G*0105N/0105N and G*0104/0104) whereas the third genotype (HLA-G*0104/0105N) was absent in the control group. HLA-G*0104/0105N genotype was interesting as it was evident in 10 patients (100%) whereas none of the fertile controls showed this genotype. Other genotypes presented in both URSA patients and fertile controls. HLA-G*0105N/0105N genotype showed the frequency (12%) in patient groups and (13%) in control groups with odds ratio (0.9126) in both groups, (30%) of the patients revealed in HLA-G*0104/ 0104 genotype whereas (27%) of the control group harbored this genotype with odds ratio 1.1587.
Role of HLA-G 14 bp polymorphism and soluble HLA-G level in recurrent spontaneous abortion
Egyptian Journal of Medical Microbiology
The immune response of the mother against her embryo is supposed to be responsible for about 50 % of recurrent spontaneous abortion (RSA) case. Objectives: To assess the prevalence of HLA-G 14bp insertion/deletion (ins/del) polymorphism in females with RSA and normal pregnant females and compare the plasma levels of soluble HLA-G (sHLA-G) in the studying groups. Also, we intended to explore the association between HLA-G 14 bp polymorphism and sHLA-G plasma levels. Methodology: This case-control study involved 50 females with RSA and 50 control pregnant females. The genotype for HLA-G 14 bp (ins/del) polymorphism was performed by PCR and their sHLA-G plasma levels were measured. Results: The HLA-G del/del genotype and ins/ins genotype frequencies were significantly different in RSA group as compared to controls (P=0.002). Additionally, the incidence of the 14-bp ins allele was significantly raised in RSA group than in control (67 vs. 41%, respectively; P=0.0004). Consequently, the higher frequency of 14-bp ins allele in RSA group as compared to controls indicate that this allele is associated with an increased risk of RSA (OR 2.9, 95% CI: 1.6-5.2, P=0.0003). Conclusion: The plasma level of sHLA-G is a promising marker in the management of RSA and could be an early indicator of the fate of In Vitro Fertilization (IVF). The polymorphism in the HLA-G gene, specifically, in the 3′UTR region of exon 8 affects the plasma level of sHLA-G and subsequent pregnancy outcome.
Human Reproduction, 2004
BACKGROUND: Previous studies have demonstrated an association between recurrent miscarriage (RM) and the maternal HLA-DRB1*01 and -DRB1*03 alleles. The primary aim of the present study was to con®rm or reject the hypothesis about this association in a larger case±control study. METHODS: HLA-DRB1, -DQA1 and -DQB1 genotyping was carried out by the PCR±sequence-speci®c primer (SSP) method in 354 patients with unexplained RM and 202 fertile controls. These results were combined with the results from a previous study of 234 RM patients and 360 controls. RESULTS: The prevalence of patients with HLA-DRB1*03 was signi®cantly increased compared with controls [odds ratio (OR) = 1.4, 95% con®dence interval (CI) = 1.1±1.9, P = 0.01, P corrected for the number of comparisons (Pc) = 0.02]. In patients with at least four previous miscarriages or with secondary RM, the association became even stronger (OR = 1.8, 95% CI = 1.3±2.5, P = 0.0005, Pc = 0.004; and OR = 1.8, 95% CI = 1.3±2.5, P = 0.0007, Pc = 0.006, respectively). There was no signi®cant differerence between patients and controls with regard to HLA-DRB1*01. CONCLUSION: The HLA-DRB1*03 allele or genes in linkage disequilibrium with it confer susceptibility to RM.
Association of genetic variants in the 3′UTR of HLA-G with Recurrent Pregnancy Loss
Human Immunology, 2016
Human Leukocyte Antigen (HLA)-G is involved in reprogramming immune responses at fetal-maternal interface during pregnancy. We evaluated the genetic diversity of the 3 0 Un-Translated Region (UTR) of HLA-G, previously associated with HLA-G mRNA post-transcriptional regulation, in women with unexplained Recurrent Pregnancy Loss (RPL), with 2 pregnancy losses (RPL-2, n = 28), or 3 or more pregnancy losses (RPL-3, n = 24), and in 30 women with a history of successful pregnancy. Results showed in RPL-2, but not in RPL-3, women compared to controls: i) higher frequency of the 14 bp Ins allele, in single and in double copy; ii) significantly lower frequency of DelG/X genotype, iii) reduced frequency of the UTR-2, and UTR-3 haplotypes; iv) higher frequencies of the UTR-5, UTR-7, and UTR-8 haplotypes. This pilot study supports the relevance of performing 3 0 UTR HLA-G genetic screening, not limited to a specific polymorphism, but considering the extended haplotypes, as a possible predictor of pregnancy outcome.
HLA-G regulatory variants and haplotypes with susceptibility to recurrent pregnancy loss
International Journal of Immunogenetics, 2018
Currently, recurrent pregnancy loss (RPL) is inconsistently defined. In several studies, RPL is defined as two or more consecutive miscarriages before 20 weeks of gestation; however, it is also defined as three uninterrupted miscarriages prior to 20 weeks of gestation (Matter & Sharif, 2016). Approximately 2% of women have RP and in about 50% of such women, the cause of the RPL remains unknown and, so, is called "idiopathic." Much of the idiopathic RPL has been postulated to be due to immunogenetic causes such as cytokine and human leucocyte antigen (HLA) genes variations (Kääriäinen, 2006;