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The miRNA processing genes play essential roles in the biosynthesis of mammalian miRNAs, and their genetic variants are involved in the development of various cancers. Our study aimed to determine the potential association between miRNA processing gene polymorphisms and cervical precancerous lesions. Five single nucleotide polymorphisms (SNPs), inc...
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Context 1
... further explore the interaction effects of gene-environment on cervical precancerous lesions, we conducted MDR amongst the combination of DICER1 rs3742330 and two other risk factors ( Table 4). The two best interac- tion models were identified (model 1: DICER1 rs3742330, passive smoking and HPV infection; model 2: DICER1 rs3742330, abortion history and HPV infection) with the highest CVC value and a significant TBA value. ...
Citations
... MicroRNAs (miRNAs) are diminutive non-coding RNAs, typically around 22 nucleotides long, and play crucial roles in post-transcriptional control of gene expression. The majority of miRNAs attach to the 3 0 untranslated region (3 0 UTR) of their target messenger RNA, leading to either its degradation or the inhibition of its translation (Huang et al., 2018). These molecular entities are posited to be ubiquitous participants in diverse biological processes, encompassing cell proliferation, differentiation, metabolic activities, developmental processes, and apoptosis (Mohammadpour-Gharehbagh et al., 2020).The activity of specific miRNAs is believed to influence around 30% of human genes. ...
... This polymorphism, particularly the A/G and G/G genotypes of rs3742330, has been associated with disturbance in DICER1 mRNA, resulting in reduced mRNA levels (Eskandari et al., 2018;Huang et al., 2018). Changes in DICER1 levels due to this polymorphism can directly affect enzyme function or indirectly influence disease development by modulating miRNA expression (Kondkar et al., 2022). ...
Background
Hypospadias continues to be a prevalent congenital anomaly affecting the male external genitalia, characterized by an unclear origin and complex treatment approaches. This study aimed to investigate the risk factors associated with hypospadias and explore its genetic link with the DICER1 rs3742330 variant.
Methods
The study involved two groups: 105 male children with hypospadias and 111 healthy male children as matched controls. Detailed history and physical examinations were conducted for all patients and controls. PCR-restriction fragment length polymorphism was utilized to identify the DICER1 rs3742330 variant, analyzing genotype distribution and allele frequency. Logistic regression analysis estimated the risk factors for hypospadias.
Results
The mean age in the hypospadias group was 4.56 ± 2.50 years. The most prevalent type of hypospadias observed was the anterior type in 60 children (57.14%). Intrauterine growth restriction, advanced maternal age, and gestational hypertension were identified as significant risk factors for hypospadias (p = .011, p = .016, and p = .041, respectively). Regarding the genetic study, no significant difference was found in both genotype and allele frequencies of the DICER1 rs3742330 variant between case and control groups.
Conclusions
The rs3742330 variant in the DICER1 gene showed no association with hypospadias cases in the Algerian population. However, multivariate logistic regression analysis identified preterm birth, low birth weight, intrauterine growth restriction, advanced maternal age, gestational diabetes, and rural residence as the most significant independent predictors for hypospadias.
... Plausibly, altered levels of DROSHA and DICER1 (as a result of these polymorphisms) may thus either directly affect enzyme function or indirectly, via differential regulation of miRNA expression profiles, can influence disease pathogenesis as discussed above. Rs3742330 polymorphism has been related to DICER1 mRNA dysregulation, wherein the polymorphic A/G and G/G genotypes harbored lower levels of DICER1 mRNA [31,69]. However, the polymorphisms rs3742330 in DICER1 and rs10719 in DROSHA were not associated with POAG and PACG or its related clinical endophenotypes (e.g., IOP and cup/disc ratio) in our Saudi cohort. ...
Aim:
In a retrospective and exploratory case-control study, we examined the genetic association of two common polymorphisms in the 3' untranslated region (UTR) of DICER1 (rs3742330) and DROSHA (rs10719) genes in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and its related clinical phenotypes in a Saudi cohort.
Methods:
DNA genotyping was performed using TaqMan real-time PCR assays in 500 participants, including 152 POAG, 102 PACG, and 246 non-glaucomatous controls. Statistical analyses were performed to examine the association(s).
Results:
Allele and genotype frequency of rs3742330 and rs10719 did not vary significantly in POAG and PACG compared to controls. No significant deviation was observed from Hardy-Weinberg Equilibrium (p > 0.05). Gender stratification revealed no significant allelic/genotype association with glaucoma types. Also, these polymorphisms showed no significant genotype effect on clinical markers such as intraocular pressure, cup/disc ratio, and the number of antiglaucoma medications. Logistic regression showed no effect of age, sex, rs3742330, and rs10719 genotypes on the risk of disease outcome. We also examined a combined allelic effect of rs3742330 (A>G) and rs10719 (A>G). However, none of the allelic combinations significantly affected POAG and PACG.
Conclusions:
The 3' UTR polymorphisms rs3742330 and rs10719 of DICER1 and DROSHA genes are not associated with POAG and PACG or its related glaucoma indices in this Middle-Eastern cohort of Saudi Arab ethnicity. However, there is a need to validate the results on a broader population and other ethnicities.
... The underlying potential mechanism(s) linking DICER1 polymorphism rs3742330 to PXG pathogenesis is unknown. Rs3742330 polymorphism has been related to dysregulation of DICER1 mRNA, wherein the polymorphic A/G and G/G genotypes harbored lower levels of DICER1 mRNA [31,32]. Altered DICER1 levels (due to polymorphism) may directly affect enzyme function or can indirectly influence disease pathogenesis via differential regulation of miRNA expression. ...
We investigated the association between DICER1 (rs3742330) and DROSHA (rs10719) polymorphisms and pseudoexfoliation glaucoma (PXG) and related clinical phenotypes in a Saudi cohort. In a retrospective case-control study, TaqMan real-time, PCR-based genotyping was performed in 340 participants with 246 controls and 94 PXG cases. The minor (G) allele frequency of rs3742330 in PXG (0.03) was significantly different from that in the controls (0.08) and protective against PXG (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.16–0.92), p = 0.017). Similarly, the rs3742330 genotypes showed a significant protective association with PXG in dominant (p = 0.019, OR = 0.38, 95% CI = 0.15–0.92), over-dominant (p = 0.024, OR = 0.39, 95% CI = 0.16–0.95), and log-additive models (p = 0.017, OR = 0.38, 95% CI = 0.16–0.92). However, none remained significant after an adjustment for age, sex, and multiple testing. Rs10719 in DROSHA did not show any significant allelic or genotype association with PXG. However, a protective effect of the GA haplotype in DICER1 and DROSHA and PXG (p = 0.034) was observed. Both polymorphisms showed no significant effect on intraocular pressure and the cup–disk ratio. In conclusion, we report a significant genetic association between variant rs3742330 in DICER1, a gene involved in miRNA biogenesis, and PXG. Further investigation in a larger group of patients of different ethnicities and functional studies are warranted to replicate and validate its potential role in PXG.
... The DICER1 rs3742330 G allele was negatively associated with the development of different types of cancer (Mohammadpour-Gharehbagh et al., 2020;Kim et al. 2019, Song et al. 2017Kim et al. 2016;Nikolic et al., 2017), precancerous cervical lesions (Huang et al. 2018) and tuberculosis (Song et al. 2013). In addition, eight articles observed positive effects on the development of tuberculosis (Cheng et al. 2018), stroke ischemia and mortality after stroke (Kim et al. 2018), preeclampsia (Eskandari et al. 2018), recurrent idiopathic pregnancy loss (Jung et al., 2014) schizophrenia (Zhou et al. 2013) and some types of cancer (Osuch-Wojcikiewicz et al. 2015;Cho et al. 2015;Liao et al. 2018). ...
... Two studies found frequencies similar to ours for DICER1 rs3742330 (Cheng et al. 2018) and DROSHA rs10719 SNPs (Nikolić et al., 2017). Moreover, positive associations were observed in 10 studies in the development of several conditions for both polymorphisms (Cheng et al. 2018;Kim et al. 2018;Eskandari et al. 2018;Yong et al., 2014;Zhou et al. 2013;Osuch-Wojcikiewicz et al. 2015;Cho et al. 2015;Liao et al. 2018;Xu et al. 2018;Gorucu et al., 2016), and negative associations were observed in 7 studies only for the DICER1 rs3742330 polymorphism (Mahammadpour-Gharehbagh et al., 2019;Kim et al. 2019;Song et al. 2017;Kim et al. 2016;Nikolic et al., 2017;Huang et al. 2018;Song et al. 2013). These discrepancies can be attributed to the interactions of genetic and/or nongenetic factors of each studied population (Angioni et al. 2020). ...
Objective
DROSHA and DICER1 enzymes participate in the main stages of microRNA synthesis. Polymorphisms can influence mRNAs stability and genes expression, and hence affect the binding of miRNAs. Thus, the present study evaluated the association of DROSHA and DICER1 polymorphisms in the development of endometriosis and other diseases.
Methods
A total of 240 endometriosis cases and 242 controls were genotyped for the DROSHA rs10719 G > A and DICER1 rs3742330 A > G polymorphisms using the TaqMan system. The association between polymorphisms and endometriosis was estimated by binary logistic regression. A literature review was also performed including all published articles (PubMed database) until December 2020, regarding the association of the studied polymorphisms and different diseases.
Results
DICER1 rs3742330GG was only found in endometriosis cases (2.1%) and deep infiltrative endometriosis (DIE) (2.5%). The DICER1 rs3742330GG genotype was significantly associated with endometriosis (P < 0.05), suggesting a tendency to present an increased risk for disease. DROSHA rs10719A and DICER1 rs3742330G allele frequencies varied among populations (6%–79% and 10.2%–55.1%, respectively). In the Brazilian population, the frequencies of these alleles were 42.3% and 7.3%, respectively. Both polymorphisms were risk factors for nonsyndromic orofacial clefts, tuberculosis, stroke ischemia and mortality after stroke, recurrent idiopathic pregnancy loss, and some types of cancer. Moreover, the DICER1 rs3742330 polymorphism was a protective factor for precancerous cervical lesions, different types of cancer and tuberculosis.
Conclusions
The results suggest that only the DICER1 rs3742330 A > G polymorphism may be associated with susceptibility to endometriosis. The frequencies of both polymorphisms were significantly different among populations, and there were discrepancies in the risk associations with the development of diseases.
... Single nucleotide polymorphism (SNP) is the most common of human heritable variants, accounting for >80% of all known polymorphisms. Huang et al. (2018) reported that AG and AG/GG genotypes in DICER1 rs3742330 reduce the risk of cervical precancerous lesions. LncRNA SNP can influence the pathology and susceptibility to many types of cancer (Yang et al., 2011). ...
Background:
The occurrence of cervical cancer is a complex process, for which human papillomavirus (HPV) infection is a risk factor, although not all women infected with HPV will develop the disease. Knockout of mammalian lung metastasis associated transcript 1 (MALAT1) is associated with increased risk for several cancer types, whereas the long non-coding RNA (lncRNA) THRIL is essential for induction of tumor necrosis factor-α expression, which plays important roles in HPV infection.
Materials and methods:
To investigate the effects of polymorphisms in the lncRNAs MALAT1 and THRIL on the susceptibility to precancerous cervical lesions, 12 single nucleotide polymorphisms (SNPs) were analyzed from 164 cervical precancerous lesion cases and 428 controls. Gene-gene and gene-environment interactions and haplotype associations were also evaluated.
Results:
We found a significantly decreased risk of precancerous cervical lesions for the THRIL rs7133268 AG genotype (odds ratio adjusted = 0.63, 95% confidence interval: 0.42-0.94, p = 0.025). Multifactor dimensionality reduction analysis identified a significant two-locus interaction model involved in HPV infection and THRIL rs7133268 (training balanced accuracy = 0.6957, testing balanced accuracy = 0.6948, cross-validation consistency = 10/10, p = 0.0046). Other SNPs, including the two identified for MALAT1, were not significantly related to the risk of precancerous cervical lesions.
Conclusion:
Our results suggest that the rs7133268 polymorphism of the lncRNA THRIL gene can reduce the genetic susceptibility of precancerous cervical lesions and in turn reduce the risk of HPV infection.
Simple Summary
Previous relations between microRNA machinery gene variants and human cancer risk have not reach the required statistical power. For the first time, the authors pooled data from 33 studies in “The Cancer Genome Atlas” database that cover 8176 pan-cancer samples which yielded 22 eligible variants within 11 genes subjected to further testing under different genetic association models, Cox regression, and trail sequential analyses. The potential roles of miRNA biogenesis genes in cancer development and prognosis have been concluded.
Abstract
Single nucleotide polymorphisms in genes involved in microRNA processing/maturation and release may deregulate the microRNAome expression levels. We aimed to assess the relationship between miRNA machinery genetic variants and human cancer risk using integrative bioinformatics analyses to identify the role of these genes in cancer aggressiveness. Mutations of 8176 pan-cancer samples were retrieved from 33 studies in “TCGA” database, and a Cox regression model for survival was performed. Next, 22 computationally identified variants within 11 genes were selected based on their high citation rate and MAF. Relevant articles through March 2020 were included. Pooled estimates under the five genetic association models were calculated. Publication bias and heterogeneity between articles were evaluated. Trial Sequential Analysis (TSA) was applied to assess the power and reliability of the draw conclusions. TCGA patients with different cancer types revealed significant alterations in miRNA machinery genes, with mutation frequency ranging from 0.6–13% of samples. RAN was associated with LN metastasis, while TARBP2 and PIWIL1 gene mutations exhibited better overall survival. In the meta-analysis, 45 articles (74,593 cases and 89,198 controls) met the eligibility criteria. Pooled analysis revealed an increased cancer risk with DROSHArs10719*G, RANrs3803012*G, DGCR8rs417309*A, and GEMIN3rs197414*A. In contrast, both DICER1rs1057035*T and GEMIN4rs2743048*G conferred protection against developing cancer. TSA showed the cumulative evidence is inadequate, and the addition of further primary studies is necessary. This study suggests a potential role of miRNA biogenesis genes in cancer development/prognosis. Further functional studies may reveal biological explanations for the differential risks of the machinery variants in different cancer types.
Background
MicroRNA (miRNA) processing machinery gene variant was associated with several diseases. We aimed to explore for the first time the association of machinery gene (DROSHA rs10719A/G; DICER1 rs3742330A/G; RAN rs14035C/T; and XPO5 rs11077T/G) variants with the susceptibility and phenotype of end‐stage renal disease (ESRD).
Method
A total of 281 participants (98 ESRD patients and 183 healthy volunteers) were enrolled. Real‐Time TaqMan allelic discrimination assay was applied for the genotyping of the specified variants. Multiple logistic regression models, univariate, multivariate, and principal component analyses were carried out.
Results
Carrying one DICER1 rs3742330*G allele conferred protection against developing ESRD [heterozygote comparison: OR = 0.30, 95% CI = 0.15‐0.62, dominant model: OR = 0.35, 95% CI = 0.17‐0.70]. Similarly, for XPO5 rs11077T/G, homozygote and heterozygote carriers of G variant were less likely to develop ESRD [homozygote comparison: adjusted OR = 0.23, 95% CI = 0.11‐0.50, and heterozygote comparison: OR = 0.50, 95% CI = 0.22‐0.92, and allelic model: OR = 0.46, 95% CI = 0.34‐0.70]. RAN rs14035*TT subjects were 5 times more likely to develop ESRD while being heterozygote (CT) have twice the risk [homozygote comparison: 5.18, 95% CI = 2.28‐11.8, heterozygote comparison: OR = 2.12, 95% CI = 1.10‐409]. Subgroup analysis also detected DICER1 rs3742330*A, XPO5 rs11077*T, and RAN rs14035*T as genetic risk determinants for ESRD development in both sex and age categories. Two genotype combinations of DROSHA/DICER1/XPO5/RAN were associated with increased susceptibility to ESRD [A‐A‐T‐T: OR = 9.49, 95%CI = 2.48‐36.31 (P = .001) and G‐A‐T‐T: OR = 5.92, 95%CI = 1.77‐19.83 (P = .004), respectively].
Conclusion
Variants and combined genotypes of DICER1 rs3742330, XPO5 rs11077, and RAN rs14035 might be associated with ESRD development in the study population. Integrating molecular analysis in ESRD risk stratification is warranted.
Association between the xeroderma pigmentosum complementation group F (XPF)rs2276466 located in the excision repair cross complementation group 4 (ERCC4) gene and cancer susceptibility has been widely investigated. However, results thus far have remained controversial. A meta-analysis was performed to identify the impact of this polymorphism on cancer susceptibility. PubMed, Embase and Science-Web databases were searched systematically up to May 20, 2018, to obtain all the records evaluating the association between the rs2276466 polymorphism and the risk of all types of cancers. We used the odds ratio (OR) as a measure of effect, and pooled the data in a Mantel-Haenszel weighed random-effects meta-analysis to provide a summary estimate of the impact of this polymorphism on gastrointestinal cancer, neurogenic cancer and other cancers (breast cancer and SCCHN). All the analyses were carried out in STATA 14.1.11 case–control studies that consisted of 5730 cases and 6756 controls, were eventually included in our meta-analysis. The significant association was observed between the XPFrs2276466 polymorphism and neurogenic cancer susceptibility (recessive model: OR = 1.648, 95% CI = 1.294–2.098, P<0.001). Furthermore, no significant impact of this polymorphism was detected on decreased gastrointestinal cancer risk (dominant model: OR = 1.064, 95%CI = 0.961–1.177, P = 0.233). The rs2276466 polymorphism might play different roles in carcinogenesis of various cancer types. Current evidence did not suggest that this polymorphism was directly associated with gastrointestinal susceptibility. However, this polymorphism might contribute to increased neurogenic cancer risk. More preclinical and epidemiological studies are still imperative for further evaluation
