Recurrent Pregnancy Loss Susceptibility Research Articles

The association of APOH and NCF1 polymorphisms on susceptibility to recurrent pregnancy loss in women with antiphospholipid syndrome.

Recurrent pregnancy loss (RPL) is the main manifestation of pathological pregnancy in antiphospholipid syndrome (APS) women. The immune state plays a significant role in the occurrence/development of APS and RPL susceptibility, but there is little research on genetic factors. Previous studies have described the important role of APOH and NCF1 in APS and pregnancy. To explore the association of APOH and NCF1 gene variants with RPL susceptibility in APS patients, we collected and analyzed 871 controls, 182 APS and RPL, and 231 RPL patients. Four single nucleotide polymorphisms (SNPs) (rs1801690, rs52797880, and rs8178847 of APOH and rs201802880 of NCF1) were selected and genotyped. We found rs1801690 (p = 0.001, p = 0.003), rs52797880 (p = 8.73e-04, p = 0.001), and rs8178847 (p = 0.001, p = 0.001) of APOH and rs201802880 (p = 3.77e-26, p = 1.31e-26) of NCF1 showed significant differences between APS and RPL patients and controls in allelic and genotype frequencies respectively. Moreover, rs1801690, rs52797880, and rs8178847 showed strong linkage disequilibrium. Especially, our results revealed a complete linkage disequilibrium (D' = 1) between rs52797880 and rs8178847. Furthermore, higher serum TP (total protein) level was described in APOH rs1801690 CG/GG (p = 0.007), rs52797880 AG/GG (p = 0.033), and rs8178847 CT/TT (p = 0.033), while the higher frequency of positive serum ACA-IgM was found in NCF1 rs201802880 GA (p = 0.017) in APS and RPL patients. Rs1801690, rs52797880, and rs8178847 of APOH and rs201802880 of NCF1 were associated with RPL susceptibility in APS patients.

Maternal Thrombophilic and Hypofibrinolytic Genetic Variants in Idiopathic Recurrent Pregnancy Loss: a Continuing Mystery.

Despite the fact that multiple recurrent pregnancy loss (RPL) etiologies have been identified, 50-70% of RPL cases remain enigmatic, and idiopathic RPL is still a serious medical challenge. A plethora of studies have investigated the correlation of RPL with variations in coagulation and/or fibrinolytic factors-encoding genes. Notwithstanding, evidence for a link between these variations and RPL remains discordant. We aimed to explore the association of thrombophilic and hypofibrinolytic gene variations with RPL development. Two hundred Saudi women were recruited in this study, comprising 150 women experiencing RPL and 50 healthy women. Thirteen genetic variants, including FV G1691A, FV A4070G, F2 G20210A, F13A1 G103T, FGB - 455G > A, PAI-1 - 675 4G/5G, ITGB3 T1565C, MTHFR C677T, MTHFR A1298C, ACE I/D, APOB G10708A, APOE T388C, and APOE C526T were genotyped using ViennaLab StripAssay. Women experiencing RPL harbor significantly higher frequencies of the F13A1 103T, FGB - 455A, and ITGB3 1565C alleles than control women (p < 0.001). No differences in the prevalence of other investigated variants were identified between control women and those with RPL. No considerable link of F5 1691G > A/4070A > G, MTHFR 677C > T/1298A > C, and APOE 388T > C/526C > T haplotypes with RPL risk was demonstrated. F13A1 G103T, FGB - 455G > A, and ITGB3 T1565C variants are connected to a higher likelihood of developing RPL and, hence, may have the potential to identify those women at risk of RPL, thereby, improving RPL susceptibility prediction. Incorporating molecular testing of thrombophilic and hypofibrinolytic genetic variants into routine workup could confer a promising approach for refined RPL risk assessment.

Association of Human forkhead box protein 3 (FOXP3) gene polymorphisms with idiopathic recurrent pregnancy loss among Kazakhstani women.

Recurrent pregnancy loss (RPL) is major pregnancy complication, with poorly defined cause.Forkhead Box P3 (FOXP3) is a transcription factor that supports Treg activation and development and attenuates immune responses. As FOXP3 production is genetically determined, we tested the association of FOXP3 gene variants with RPL. A retrospective case-control study, performed between April 2019 and February 2020. Study subjects comprised 62 RPL cases and 60 control women. Genotyping of the four FOXP3 variants rs2294021 (T>C), rs2232365 (G>A), rs3761548 (C>A), and rs141704699 (C>T) was done by real-time PCR, with defined clusters. Logistic odds ratios (ORs) of RPL risk were estimated with 95% confidence interval (CI) after adjustment; statistical significance set at P<0.05. Minor allele frequency (MAF) of rs2294021 was significantly lower [P<0.001; OR(95% CI)=0.25(0.11-0.55)], while rs2232365 MAF was significantly higher [P=0.045; OR(95% CI)=1.85(1.05-3.28)] in cases, hence assigning RPL-protection and -susceptibility to these variants, respectively. Increased RPL risk was seen in rs2232365 homozygous minor allele carrying genotype [OR(95% CI)=5.14(1.01-26.15)], while reduced RPL risk was noted in rs2294021 heterozygous [OR(95% CI)=0.30(0.11-0.80)], and homozygous minor allele [OR(95% CI)=0.10(0.01-0.83)] genotype carriers. Moderate linkage disequilibrium analysis was seen between the tested variants. Increased frequency of TACC, and reduced frequency of CGAC haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection to these haplotypes, respectively. These results suggest that FOXP3 variants and haplotypes are associated with idiopathic RPL, suggesting the likely contribution of Treg to RPL.

Association of miR-146a and miR196a2 genotype with susceptibility to idiopathic recurrent pregnancy loss in Iranian women: A case-control study.

BackgroundRecurrent pregnancy loss (RPL) is the most common complaint of pregnancy in females with a prevalence of 5%. Numerous documents have shown that single nucleotide polymorphisms are able to change miRNA transcription and/or maturation, which may alter the incidence of disorders such as RPL.ObjectiveTo assess the relationship of miR-146aC G (rs2910164) and miR-196a2T C (rs11614913) with RPL susceptibility in Iranian women.Materials and MethodsBlood samples were collected from 214 women who had experienced at least two consecutive spontaneous miscarriages (case) and 147 normal individuals without a history of miscarriage (control). MiR-146aC G and miR-196a2T C genotypes were evaluated via the restriction fragment length polymorphism technique.ResultsThe genotypes incidence did not show a significant difference in pre-miR-146aC G polymorphism CC vs CG + GG (p = 0.854; OR = 0.933; 95% CI) and CC + CG vs GG (p = 0.282; OR = 1.454; 95% CI). Also, no significant difference was observed between pre-miR-196a2T C polymorphism TT vs TC + CC (p = 0.862; OR = 0.938; 95% CI) and TT + TC vs CC and (p = 0.291; OR = 1.462; 95% CI) in both the case and control groups.ConclusionThe results showed that although the distribution of miR-146aC G and miR-196a2T C was different between the unknown RPL and control groups, these variances were not statistically significant.

Association of Two MMP-8 Gene Polymorphisms With Recurrent Pregnancy Loss in Iranian Women

Background: It has been reported that less than 5% of women experience recurrent pregnancy loss (RPL). different matrix metalloproteinases (MMPs) have proteolysis function with a main role in the stable development of the fetus. Objective: This study aims to assess the associations between two single nucleotide polymorphisms (rs2509013 C&gt;T and rs11225395 G&gt;A) of MMP-8 gene and RPL among 130 Iranian women with a history of RPL and 130 controls. Methods: Genotyping of the MMP-8 gene was done for the two polymorphisms by using Sanger sequencing method. Results: High frequency of AA genotype (OR: 2.5, 95%CI:1.02-4.1, P&lt;0.01) and A allele (OR:1.95, 95% CI:0.95-3.1, P&lt;0.001) of rs11225395 G&gt;A polymorphism in patients compared to controls. This high frequency was also reported in the haplotypes and combined genotypes of polymorphism. Conclusion: The MMP-8 gene may be involved in RPL risk and is a potential biomarker for RPL susceptibility.

Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study.

We assessed the predictive ability of a combined genetic variant panel for the risk of recurrent pregnancy loss (RPL) through a case-control study. Our study sample was from Ukraine and included 114 cases with idiopathic RPL and 106 controls without any pregnancy losses/complications and with at least one healthy child. We genotyped variants within 12 genetic loci reflecting the main biological pathways involved in pregnancy maintenance: blood coagulation (F2, F5, F7, GP1A), hormonal regulation (ESR1, ADRB2), endometrium and placental function (ENOS, ACE), folate metabolism (MTHFR) and inflammatory response (IL6, IL8, IL10). We showed that a genetic risk score (GRS) calculated from the 12 variants was associated with an increased risk of RPL (odds ratio 1.56, 95% CI: 1.21, 2.04, p = 8.7 × 10−4). The receiver operator characteristic (ROC) analysis resulted in an area under the curve (AUC) of 0.64 (95% CI: 0.57, 0.72), indicating an improved ability of the GRS to classify women with and without RPL. Ιmplementation of the GRS approach can help define women at higher risk of complex multifactorial conditions such as RPL. Future well-powered genome-wide association studies will help in dissecting biological pathways previously unknown for RPL and further improve the identification of women with RPL susceptibility.

Variants c.677 C>T, c.1298 A>C in MTHFR, and c.66 A>G in MTRR Affect the Occurrence of Recurrent Pregnancy Loss in Chinese Women.

Objective: Although genetic variants of key enzymes in the folic acid-methionine metabolic circulation, including methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) were thought to be related to the risk of recurrent pregnancy loss (RPL), the results of recent studies have been inconsistent. Therefore, the present retrospective case–control study was designed to explore whether the variants c.66A>G in MTRR and c.677C>T and c.1298A>C in MTHFR are associated with the susceptibility of RPL in Southeast Chinese women.Materials and Methods: In total, samples from 237 RPL patients and 618 healthy controls were collected and genotyped by fluorescent quantitative polymerase chain reaction. The frequencies of the variants were calculated and compared between the two groups. The relative risk of the various genotypes was further determined by calculating the odds ratio (OR) at a 95% confidence interval (CI).Results: A significant positive correlation was observed between the variants MTHFR c.677C>T, MTHFR c.1298A>C, MTRR c.66A>G, and RPL susceptibility (MTHFR c.677C>T, OR = 0.74, 95% CI = 0.58–0.95, p = 0.02; MTHFR c.1298A>C, OR = 1.39, 95% CI = 1.09–1.77, p = 0.008; MTRR c.66A>G, OR = 1.38, 95% CI = 1.10–1.73, p = 0.006). Further analysis of the genotypic distributions of the three variants between the two groups showed that the MTHFR c.677C>T heterozygote was associated with lower RPL risk, while the MTHFR c.1298A>C variant and MTRR c.66A>G heterozygote were correlated with higher RPL risk (dominant model, MTHFR c.677C>T, OR = 0.70, 95% CI = 0.52–0.95, p = 0.02; MTHFR c.1298A>C, OR = 1.39, 95% CI = 1.03–1.88, p = 0.032; MTRR c.66A>G, OR = 1.62, 95% CI = 1.20–2.19, p = 0.002).Conclusion: MTHFR c.677C>T and c.1298A>C and MTRR c.66A>G were associated with RPL in Southeast Chinese women.

Maternal HLA-DR, HLA-DQ, and HLA-DP loci are linked with altered risk of recurrent pregnancy loss in Lebanese women: A case-control study.

We investigated the association between idiopathic recurrent pregnancy loss (RPL) and HLA-DPB1, HLA-DQB1, and HLA-DRB1 alleles and DPB1-DQB1-DRB1 haplotypes. Case-control retrospective study involved 93 Lebanese women with unexplained RPL, and 113 multiparous Lebanese women with two or more successful pregnancies, and no miscarriages who served as controls. DPB1, DQB1, and DRB1 genotyping was performed by PCR-SSP. Expected and observed DRB1, DQB1, and DPB1 frequencies were comparable, and HLA genotype frequencies were in Hardy-Weinberg equilibrium. Significantly higher frequencies of DRB1*04:01:01 and DRB1*08:01:01, and decreased DRB1*07:01:01 frequency were seen in RPL cases than in controls. On the other hand, the distribution of DQB1 alleles was comparable between cases and control groups. Significantly lower frequencies of DPB1*04:01:01 and DPB1*14:01:01 were seen in women with RPL than control subjects. While the frequency DPB1*02:01:01 was markedly higher in RPL cases than in controls, the difference was not significant. DPB1-DQB1-DRB1 haplotype analysis identified haplotype DPB1*04:01:01-DQB1*03:02:01-DRB1*04:01:01 to be positively associated, while haplotype DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 to be negatively associated with RPL. Of these two haplotypes, only DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 remained significant after correction for multiple tests (Pc =.0008). Our results confirm an association of select DRB1 and DPB1 alleles with RPL in Lebanese women, and the first to identify DPB1-DQB1-DRB1 linked with altered RPL susceptibility, further highlighting the immunological/inflammatory nature of RPL.

3'-UTR Polymorphisms in the Vascular Endothelial Growth Factor Gene (VEGF) Contribute to Susceptibility to Recurrent Pregnancy Loss (RPL).

Numerous studies have examined the genetic association of vascular endothelial growth factor (VEGF) single nucleotide polymorphisms (SNPs) with recurrent pregnancy loss (RPL). However, of the four known SNPs in the 3′-untranslated region (3′-UTR) of VEGF, three SNPs—namely rs3025040 (1451C>T), rs10434 (1612G>A), and rs3025053 (1725G>A)—remain poorly characterized with regard to RPL. Herein, we evaluated the association between these three SNPs in the VEGF 3′-UTR and RPL susceptibility. We analyzed VEGF 3′-UTR gene variants in with and without RPL using TaqMan allelic discrimination. There were significant differences in the genotype frequencies of 1612G>A (GA: adjusted odds ratio (AOR), 0.652; 95% confidence interval (CI), 0.447–0.951; p = 0.026) and 1725G>A (GA: AOR, 0.503; 95% CI, 0.229–0.848; p = 0.010) in RPL patients vs. controls. Our results indicate that the 1612G>A and 1725G>A polymorphisms in the 3′-UTR of VEGF are associated with RPL susceptibility in Korean women. These data suggest that VEGF 3′-UTR polymorphisms may be utilized as biomarkers for the detection of RPL risk and prevention.

Association Study between the Polymorphisms of Matrix Metalloproteinase (MMP) Genes and Idiopathic Recurrent Pregnancy Loss.

Recurrent pregnancy loss (RPL) refers to two or more consecutive pregnancy losses. It is estimated that fewer than 5% of women experience RPL. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play important roles in providing a safe and conducive environment for the stable development of the fetus. In this case-control study, we evaluated the associations between RPL and single nucleotide polymorphisms (SNPs) in MMP-8 and MMP-27. We recruited 375 Korean women with a history of RPL and 240 ethnically-matched healthy parous controls, and we performed genotyping for the MMP-8 rs2509013 C>T, MMP-8 rs11225395 G>A, and MMP-27 rs3809017 T>C polymorphisms. All SNPs were genotyped via the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. In the genotype frequency analyses, the TT genotype of the MMP-8 rs2509013 C>T (age-adjusted odds ratio, 0.415; 95% confidence interval, 0.257–0.671; P = 0.0003) and TC genotype of MMP-27 rs3809017 T>C (age-adjusted odds ratio, 0.681; 95% confidence interval, 0.483–0.961; P = 0.029) were associated with decreased RPL susceptibility. Moreover, these trends were maintained in the haplotype and genotype combination analyses. Interestingly, amongst the RPL patients, higher levels of homocysteine (P = 0.042) and uric acid (P = 0.046) were associated with MMP-27 rs3809017 T>C. In conclusion, the two polymorphisms of MMP-8 and MMP-27 were significantly associated with RPL risk, both individually and in combination. Therefore, these two polymorphisms are potential biomarkers for RPL susceptibility.

The role of FAS, FAS-L, BAX, and BCL-2 gene polymorphisms in determining susceptibility to unexplained recurrent pregnancy loss.

Idiopathic recurrent pregnancy loss (RPL) is a multifactorial reproductive disorder where an impaired control of apoptosis is likely involved. Triggering the cell death mechanism occurs in a spatiotemporal manner and is strongly related to a healthy pregnancy. Single nucleotide polymorphisms (SNPs) at the regulatory regions of genes are known to influence the expression patterns of apoptosis-related molecules. A total of 296 unrelated female Brazilian patients were evaluated for clinical-demographic variables and genetic factors: 140 women who had experienced an unexplained RPL (with at least two consecutive abortions) and 156 healthy multiparous women. In all patients, six SNPs were evaluated in genes of apoptosis-related pathways: FAS (rs2234767, rs1800682), FAS-L (rs763110, rs5030772), BAX (rs4645878), and BCL-2 (rs2279115) by PCR followed by a restriction fragment length polymorphism (RFLP)-based analysis. The BAX-248GA genotype is independently associated with idiopathic RPL [adjusted OR = 0.30, 95% CI 0.13-0.70, P= 0.005] susceptibility. In the same multivariate model, the variables ethnicity, smoking, and alcohol consumption were statistically associated with RPL susceptibility (P< 0.05). No association with RPL susceptibility was reported for the remaining SNPs. Our study is the first to evaluate the role of the main SNPs from both the extrinsic and intrinsic apoptosis pathways in RPL susceptibility. The association of BAX-248G/A with RPL susceptibility suggests that maternal predisposition for RPL has an essential contribution from genes involved in the delicate balance of endometrium cell turnover (cell death/proliferation). Therefore, apoptotic genes may represent promising targets for future studies on healthy pregnancies and the spectrum of pregnancy disorders.

Association among cytotoxic T-lymphocyte antigen 4 gene, rs231775 polymorphism, and recurrent pregnancy loss risk.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is expressed constitutively on regulatory T cells. So far, several studies have focused on association between CTLA-4 gene polymorphisms and recurrent pregnancy loss (RPL). However, above association between the CTLA-4 gene polymorphism and RPL susceptibility is uncertain. Therefore, we performed a timely meta-analysis of all current publications to clarify this relationship. We located articles from the PubMed and Chinese language (WanFang) databases that were published up until July 25, 2018. Finally, we obtained six case–control studies, containing 2405 total cases and 2607 total controls, based on search criteria for abortion susceptibility related to the CTLA-4 +49 G/A polymorphism. The odds ratios (OR) and 95% confidence intervals (CIs) revealed association strengths. There was significantly decreased association between this polymorphism and whole population risk (e.g. AA vs. GG: OR = 0.56, 95% CI = 0.38–0.81, P=0.002). Additionally, in ethnicity subgroups, similar association was found both in China (e.g. AA vs. GG: OR = 0.49, 95% CI = 0.39–0.63, P=0.002) and non-China (e.g. AG vs. GG: OR = 0.46, 95% CI = 0.34–0.63, P<0.001). Current analysis suggested CTLA-4 +49 G/A polymorphism may weakly decrease RPL risk for women of childbearing age.

The interaction effect of angiogenesis and endothelial dysfunction-related gene variants increases the susceptibility of recurrent pregnancy loss

The role of genetic polymorphisms in the pathogenesis of recurrent pregnancy loss (RPL) has been studied intensively. Complex diseases, including miscarriage, are believed to have a polygenic basis, and gene-gene interactions can play a significant role in the etiology of the disease. This study was conducted to investigate the association of gene-gene interactions with angiogenesis, endothelial dysfunction-related gene polymorphisms, and RPL. A case-control study was conducted with 253 unrelated RPL patients with 2 or more spontaneous pregnancy losses and 339 healthy women with no history of pregnancy complications. Genotyping of single-nucleotide polymorphisms (SNPs) was performed using real-time polymerase chain reaction (real-time PCR), restriction fragment length polymorphism (RFLP), or allele-specific polymerase chain reaction methods. The genotypes 677TT of the MTHFR gene, 936TT, 936CT, and 634CC, 634GC of the VEGF gene, and allele 894T of the NOS3 gene were associated with a predisposition to RPL in the Russian population. A significant role of additive and epistatic effects in the gene-gene interactions of the SNPs of SERPINE-1, ACE, NOS3, MTHFR, and VEGF genes in RPL was demonstrated. The results showed that gene-gene interactions are important for RPL susceptibility. Additionally, analysis of the genotype combinations of several allelic variants provides more information on RPL risk than analysis of independent polymorphic markers.

Association of adiponectin gene variants with idiopathic recurrent miscarriage according to obesity status: a case\u2013control study

BackgroundThis study addresses whether the association of adiponectin gene (ADIPOQ) variants with idiopathic recurrent pregnancy loss (RPL) is influenced by obesity.MethodsRetrospective case–control study performed in outpatient obstetrics/gynecology clinics. Study subjects comprised 308 women with RPL, defined as ≥ 3 consecutive miscarriages of unknown etiology, and 310 control women. ADIPOQ genotyping was done by allele exclusion method on real-time PCR.ResultsOf the 14 ADIPOQ variants tested, the minor allele frequency (MAF) of rs4632532, rs17300539, rs266729, rs182052, rs16861209, and rs7649121 were significantly higher, while rs2241767, and rs1063539 MAF were lower in RPL cases, hence assigning RPL-susceptibility and protection to these variants, respectively. Higher frequencies of heterozygous rs17300539 and rs16861209, and homozygous rs4632532, rs266729, and rs182052 genotypes, and reduced frequencies of heterozygous rs1063539 and rs2241767, homozygous rs2241766 genotypes were seen in RPL cases. ADIPOQ rs4632532, and rs2241766 were associated with RPL in obese, while rs1063539 and rs16861209 were associated with RPL in non-obese women; rs182052 and rs7649121 associated with RPL independently of BMI changes. Based on LD pattern, two haplotype blocks were identified. Within Block 1 containing rs4632532, rs16861194, rs17300539, rs266729, rs182052, rs16861209, rs822396, and rs7649121, increased frequency of CAGGACAT and TAACGAAA, and reduced frequency of TAGCGCAA haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection, respectively.ConclusionThis is the first study to document contribution of ADIPOQ variants and haplotypes with RPL, and also to underscore the contribution of obesity to genetic association studies.

Association between Thrombophilic Genes Polymorphisms and Recurrent Pregnancy Loss Susceptibility in the Iranian Population: a Systematic Review and Meta-Analysis

Studies have indicated that thrombophilic genes polymorphisms are associated with recurrent pregnancy loss (RPL) in the Iranian population. We aimed to evaluate the precise association between thrombophilic genes polymorphisms (MTHFR C677T, MTHFR A1298C, Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G) and RPL risk in the Iranian population. PubMed, Web of Science, Google Scholar, and ISC were searched for eligible articles published up to April 1, 2017. In total, 37 case-control studies in 18 relevant publications were selected: 1,199, 1,194, 630, 830, and 955 RPL cases and 1,079, 1079, 594, 794, and 499 controls for MTHFR C677T, MTHFR A1298C,Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G, respectively. The results indicated a significant increased risk of RPL in all genetic models in the population. Also, Prothrombin G20210A and FVL G1691A as well as PAI-1 4G/5G polymorphisms were associated with RPL risk in the Iranian population. Hence, thrombophilic genes polymorphisms are associated with an increased RPL risk in the Iranian population.

Meta-analyses of associations between interleukin-10 polymorphisms and susceptibility to recurrent pregnancy loss

ObjectiveThe aim of this study was to investigate whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to recurrent pregnancy loss (RPL). MethodsWe conducted a literature search using the PubMed and EMBASE databases and performed meta-analyses on the associations between IL-10 −1082 G/A, −819 C/T, and −592 C/A polymorphisms and RPL, using fixed- or random-effects models. ResultsA total of 15 papers involving 1858 RPL patients and 1949 controls were considered in this study. Meta-analysis of IL-10 −1082 G/A polymorphism revealed no association between RPL and the IL-10 −1082 G allele (OR=0.999, 95% CI=0.815–1.223, p=0.989). However, meta-analysis of IL-10 −819 C/T polymorphism in all study subjects revealed an association between RPL and the IL-10 −819 C allele (OR=0.680, 95% CI=0.498–0.927, p=0.015). Stratification by ethnicity indicated an association between the IL-10 −819 C allele and RPL in the Asian group (OR=0.421, 95% CI=0.226–0.783, p=0.006), but not in the Caucasian and Arab groups (OR=1.053, 95% CI=0.218–5.077, p=0.949, and OR=0.800, 95% CI=0.606–1.081, p=0.152, respectively). Furthermore, a relationship between the IL-10 −592 C allele and RPL was identified in the Asian group (OR=0.763, 95% CI=0.633–0.919, p=0.004), but not in the Caucasian and Arab groups. ConclusionsThe meta-analyses demonstrate that IL-10 −819 C/T and −592 C/A polymorphisms are associated with RPL susceptibility in Asian women, but not in the Caucasian and Arab populations.

Interleukin-1beta -511T>C genetic variant contributes to recurrent pregnancy loss risk and peripheral natural killer cell proportion

To identify whether interleukin gene polymorphisms are risk factors for idiopathic recurrent pregnancy loss (RPL) in Korean women. Case-control study. Hospital-based study. A cohort of 385 idiopathic RPL patients and 232 controls with Korean ethnicity. None. Genotyping was assessed with a polymerase chain reaction-restriction fragment length polymorphism assay. We examined polymorphisms in three interleukin (IL) genes: IL-1β, IL-4, and IL-10. The IL-1β -511T>C polymorphism was associated with RPL (-511TT vs. -511CC: adjusted odds ratio 1.826; 95% confidence interval 1.130-2.953). Allelic gene-gene interaction analysis revealed that the T/B2/G (IL-1β/IL-4/IL-10) allele combination was only detected in the RPL group (adjusted odds ratio 20.046; 95% confidence interval 1.188-338.204). The proportion of peripheral natural killer cells was higher in patients with the IL-1β -511C allele compared with the -511T allele. According to these results, IL-1β -511T>C may be a predisposing factor to RPL susceptibility. However, the mechanism underlying the function of IL-1β -511T>C in RPL remains to be determined, and further studies are needed to improve understanding of the roles of IL-1β -511T>C, using a larger and more heterogeneous cohort.