Haplotype-based association of two SNPs in miR-423 with unexplained recurrent pregnancy loss in a Chinese Han population (original) (raw)
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A microRNA-520 mirSNP at the MMP2 gene influences susceptibility to endometriosis in Chinese women
Journal of Human Genetics, 2013
The MMP2 gene has been implicated in the pathogenesis of endometriosis. We investigated the role and function of single-nucleotide polymorphisms (SNP) of MMP2 in relation to endometriosis. First a case-control study was conducted and 17 SNPs were examined in 211 patients and 344 controls. Regression analysis was used to evaluate the genetic effect. We used reporter assay to validate the functional consequences of the significant SNP. Two SNPs (rs243832 and rs7201) had P-values o0.05 and they are in strong linkage disequilibrium (D 0 ¼ 0.96 and r 2 ¼ 0.47). Further analysis showed that rs7201 but not rs246832 was an independent risk factor and the risk C allele of rs7201 had an odds ratio (OR) of 1.88 (P ¼ 0.004). SNP rs7201 is located at the 3 0-untranslated region and is predicted to be within the microRNA-520g binding site. The reporter assay for rs7201 showed that the risk C allele had a higher expression level than the A allele (P ¼ 0.027). Using microRNA-520g mimic and inhibitor, the results indicated that the A allele but not the risk C allele can be regulated by microRNA-520g. The C allele of SNP rs7201 increases a risk for endometriosis because of out of regulation by microRNA-520g.
Disease Markers, 2022
It has been established that microRNAs (miRNAs) are involved in the regulation of immune responses and serve as biomarkers of inflammatory diseases as well as recurrent spontaneous miscarriage (RSM). Herein, we aimed to study the relationship between three functional miR146a gene polymorphisms with idiopathic RSM (IRSM) susceptibility. We recruited 161 patients with IRSM and 177 healthy women with at least one live birth and without a history of abortion. Genotyping was performed using RFLP-PCR and ARMS-PCR methods. We found that the rs6864584 T/C decreased the risk of IRSM under dominant TT+TC vs. CC (OR = 0:029) and allelic C vs. T (OR = 0:028) contrast models. Regarding rs2961920 A/C and rs57095329 A/G polymorphisms, the enhanced risk of IRSM was observed under different genetic contrasted models, including the codominant CC vs. AA (OR = 2:81 for rs2961920) and codominant GG vs. AA (OR = 2:36 for rs57095329). After applying a Bonferroni correction, haplotype analysis revealed a 51% decreased risk of IRSM regarding the ACA genotype combination. This is the first study reporting that miR146a rs57095329 A/G, rs2961920A/C, and rs6864584 T/C polymorphisms are associated with the risk of IRSM in a southern Iranian population. Performing replicated case-control studies on other ethnicities is warranted to outline the precise effects of the studied variants on the risk of gestational trophoblastic disorders.
International Journal of Reproductive BioMedicine (IJRM)
Background: Recurrent 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. Objective: To assess the relationship of miR-146aC > G (rs2910164) and miR-196a2T > C (rs11614913) with RPL susceptibility in Iranian women. Materials and Methods: Blood 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. Results: The 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...
miRNAs can be generally associated with human pathologies as exemplified for miR-144*
BMC Medicine, 2014
Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR.
Genetic variability of microRNA regulome in human
Molecular Genetics & Genomic Medicine, 2014
MicroRNAs are currently being extensively studied due to their important role as post-transcriptional regulators. During miRNA biogenesis, precursors undergo two cleavage steps performed by Drosha-DGCR8 (Microprocessor) cleaving of pri-miRNA to produce pre-miRNA and Dicer-mediated cleaving to create mature miRNA. Genetic variants within human miRNA regulome have been shown to influence miRNA expression, target interaction and to affect the phenotype. In this study, we reviewed the literature, existing bioinformatics tools and catalogs associated with polymorphic miRNA regulome, and organized them into four categories: (1) polymorphisms located within miRNA genes (miR-SNPs), (2) transcription factor-binding sites/miRNA regulatory regions (miR-rSNPs), (3) miRNA target sites (miR-TS-SNPs), and 4. miRNA silencing machinery (miR-SM-SNPs). Since the miR-SM-SNPs have not been systematically studied yet, we have collected polymorphisms associated with miRNA silencing machinery. We have developed two catalogs containing genetic variability within: (1) genes encoding three main catalytic components of the silencing machinery, DROSHA, DGCR8, and DICER1; (2) miRNA genes itself, overlapping Drosha and Dicer cleavage sites. The developed resource of polymorphisms is available online (http://www.integratomics-time.com/miR-NA-regulome) and will be useful for further functional studies and development of biomarkers associated with diseases and phenotypic traits.
Volume 18, Issue 4, October , 2024
Background: Circulating microRNAs (miRNAs or miRs) are key regulators of a wide array of biological processes that aberrantly express under physiological as well as pathological conditions. This study aims to determine whether altered expression of circulating miR-223-3p in plasma is associated with an increased risk of idiopathic recurrent pregnancy loss (iRPL), and if it could be a novel non-invasive biomarker for diagnosis of iRPL. Materials and Methods: In this case and control study, Plasma samples were obtained from 60 women with a history of ≥ 2 consecutive miscarriages and 60 women with at least one full-term pregnancy and no history of miscarriage. The samples were used to assess the expression of circulating miR-223-3p by quantitative real-time polymerase chain reaction (qPCR) and determine the correlation between patient clinico-demographic parameters and miR-223-3p expression levels. We used receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic accuracy of miR-223-3p for the diagnosis of iRPL. Results: There was significant up-regulation in miR-223-3p expression in patients with iRPL compared with healthy controls (P=0.002). No significant correlation was found between the expression level of miR-223-3p and the number of miscarriages in iRPL patients (P=0.344). ROC curve analysis revealed that the area under the curve (AUC) value for miR-223-3p was 0.658 [95% confidence interval (95% CI): 0.5590.757, P=0.002). Conclusion: These results suggest that a higher expression level of circulating miR-223-3p may be closely related with the increased risk of iRPL and possibly serve as a promising non-invasive diagnostic biomarker for iRPL.
Gene Reports, 2017
Background and purpose: MicroRNAs (miRNAs) have been appointed as potential biomarkers for gastric cancer. Recent evidences suggest that single-nucleotide polymorphisms (SNPs) in miRNAs may change the miRNA biogenesis and influence cancer susceptibility. The aim of this study was to investigate the association of Mir-SNPs in miR-27a rs895819, miR-125a rs12976445, miR-196a2 rs11614913, miR-499 rs3746444, and miR-605 rs2043556 and their effect, alone and combined, on gastric cancer risk. Methods: DNA samples obtained from 151 gastric cancer (GC) patients and 249 non-cancer subjects (control) were genotyped using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique or the TaqMan® SNP Genotyping Assay. Multiple logistic regression analysis was used to assess the associations between the miRNA polymorphisms and GC risk according to log-additive, dominant, and recessive models. Combined genotype analyses were also performed, using Fisher's exact test. Results: The Mir-SNPs miR-27a rs895819, miR-125a rs12976445 and miR-499 rs3746444 were not associated with risk of GC. However, the miR-196a2 rs11614913 TT variant genotype was associated with a significantly increased risk for GC in the recessive model (OR = 2.88; 95% CI = 1.45-5.72; P = 0.002), and miR-605 rs2043556 AG and GG genotype carriers showed a significantly higher risk for GC in both the dominant (adjusted OR= 1.79; 95% CI= 1.14-2.82; P = 0.001) and the log-additive models (OR= 1.46; 95% CI= 1.01-2.12; P = 0.044). The combined genotype analysis showed that the presence of the three risk genotypes miR-27a G / miR-125a C / miR-605 G is associated with higher risk of GC (OR = 11.00; 95% CI = 1.13-106.5; P = 0.046). In addition, the combined genotype analysis of only miR-196a2 rs11614913 and miR-605 rs2043556 revealed that individuals carrying both risk alleles (miR-196a2 T / miR-605 G) also presented a significantly higher risk for GC compared to double wild-type homozygous individuals (OR = 2.00; 95% CI = 1.08-3.71; P = 0.031). Conclusions: Our data showed that miR-196a2 rs11614913 and miR-605 rs2043556, alone or in combination, modulate the risk of developing GC in a Brazilian population, and that the combined genotypes miR-27a G / miR-125a C / miR-605 G may potentiate this risk.
The Prostate, 2009
A G > C polymorphism (rs2910164) which is located in the sequence of miR-146a precursor, results in a change from a G:U pair to a C:U mismatch in its stem region. To explore whether rs2910164 plays any role in prostate cancer (CaP), we analyzed the association between miR-146a polymorphism and risk of CaP and the expression of miR-146a with different genotypes in CaP tissues in southern Chinese Han population. MATERIALS AND METHODS. Two hundred fifty-one CaP and 280 control subjects were included in the cancer association study, and 15 CaP tissue samples were used to test the expression of the miRNA precursors by real-time quantitative reverse transcription PCR. RESULTS. We found that subjects carrying CC homozygotes had a 0.65-fold reduced risk (95% CI ¼ 0.43-0.99) than those carrying GG/GC genotypes (P ¼ 0.03), and the C allele displayed a lower prevalence of CaP compared with the G allele (OR ¼ 0.73, 95% CI ¼ 0.57-0.94, P ¼ 0.01). Moreover, hsa-miR-146a quantification showed that homozygous carriers of the C-variant had significantly decreased miRNA levels compared to the carriers of the GG/GC genotype. CONCLUSIONS. The natural genetic variation in pre-miR-146a affects the amount of mature miR-146a, contributes to the genetic predisposition to CaP.
Journal of Clinical Medicine
Pregnancy is controlled by several types of genes and the regulation of their expression is tightly controlled by miRNAs. The present study was carried out to explore the association between miR-125a polymorphic sequence variation and its expression and recurrent pregnancy loss (RPL) compared to full-term healthy controls. A total of 150 women that had experienced two or more RPLs and 180 healthy controls (two or more full-term pregnancies) were recruited, along with 50 product of conception (POC) samples from the corresponding RPL patients, and evaluated for miR-125a SNPs by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), which was confirmed by high resolution melting (HRM)/DNA sequencing. Additionally, the expression of miR-125a was quantified with q–PCR in the maternal plasma of 40 corresponding RPL patients against healthy controls. The frequency of variant genotype CC was significantly higher in RPL cases (19.3%) than controls (10.5%), ...
Carcinogenesis, 2008
A G > C polymorphism (rs2910164) is located in the stem region opposite to the mature miR-146a sequence, which results in a change from G:U pair to C:U mismatch in the stem structure of miR-146a precursor. Here, we elucidated the biological significance of this polymorphism, based on cancer association study and cell model system. The cancer association study included 479 hepatocellular carcinoma (HCC) and 504 control subjects. We found that the genotype distribution of this polymorphism in HCC cases was significantly different from that in control subjects (P 5 0.026). The association between the genotype and the risk of HCC was further analyzed using multivariate unconditional logistic regression, with adjustment for sex, age and hepatitis B virus status. The results revealed that male individuals with GG genotype were 2-fold more susceptible to HCC (odds ratio 5 2.016, 95% confidence interval 5 1.056-3.848, P 5 0.034) compared with those with CC genotype. We next examined the influence of this polymorphism on the production of mature miR-146a and found that G-allelic miR-146a precursor displayed increased production of mature miR-146a compared with C-allelic one. Further investigations disclosed that miR-146a could obviously promote cell proliferation and colony formation in NIH/ 3T3, an immortalized but non-transformed cell line. These data suggest that the G > C polymorphism in miR-146a precursor may result in important phenotypic traits that have biomedical implications. Our findings warrant further investigations on the relation between microRNA polymorphism and human diseases.