DICER1 Rs3742330 Research Articles

Impacts of DROSHA (rs10719) and DICER (rs3742330) Variants on Breast Cancer Risk and Their Distribution in Blood and Tissue Samples of Egyptian Patients.

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression and play critical roles in tumorigenesis. Genetic variants in miRNA processing genes, DROSHA and DICER, have been implicated in cancer susceptibility and progression in various populations. However, their role in Egyptian patients with breast cancer (BC) remains unexplored. This study aims to investigate the association of DROSHA rs10719 and DICER rs3742330 polymorphisms with BC risk and clinical outcomes. This case-control study included 209 BC patients and 106 healthy controls. Genotyping was performed using TaqMan assays in blood, tumor tissue, and adjacent non-cancerous tissue samples. Associations were analyzed using logistic regression and Fisher's exact test. The DROSHA rs10719 AA genotype was associated with a 3.2-fold increased risk (95%CI = 1.23-9.36, p < 0.001), and the DICER rs3742330 GG genotype was associated with a 3.51-fold increased risk (95%CI = 1.5-8.25, p = 0.001) of BC. Minor allele frequencies were 0.42 for rs10719 A and 0.37 for rs3742330 G alleles. The risk alleles were significantly more prevalent in tumor tissue than adjacent normal tissue (rs10719 A: 40.8% vs. 0%; rs3742330 G: 42.7% vs. 0%; p < 0.001). However, no significant associations were observed with clinicopathological features or survival outcomes over a median follow-up of 17 months. In conclusion, DROSHA rs10719 and DICER rs3742330 polymorphisms are associated with increased BC risk and more prevalent in tumor tissue among our cohort, suggesting a potential role in miRNA dysregulation during breast tumorigenesis. These findings highlight the importance of miRNA processing gene variants in BC susceptibility and warrant further validation in larger cohorts and different ethnic populations.

Polymorphisms in MicroRNA Biogenesis Genes and the Risk of Preeclampsia in Jordan

Abstract Background: Preeclampsia (PE) is a serious pregnancy condition with a complex etiology involving both environmental and genetic factors. This study investigated the association between polymorphisms in the microRNA (miRNA) biogenesis genes DICER (rs3742330) and RAN (rs14035) and the risk of PE among Jordanian women. Methods: A total of 224 pregnant Jordanian women were recruited. Genotypes of rs3742330 and rs14035 were determined using polymerase chain reaction techniques. This was a cross-sectional case–control study conducted in Jordan. Genotype and allele frequencies were compared using Chi-square tests, and hematological parameters were compared using t-tests. Results: The G allele and AG/GG genotypes of rs3742330 were more frequent in the PE group than controls (P &lt; 0.05). However, no association was found between rs14035 and PE. Higher body mass index (BMI) was associated with increased PE risk (P &lt; 0.001). Conclusion: The DICER rs3742330 polymorphism and increased BMI were associated with PE in Jordanian pregnant women. This suggests that genetic variations in miRNA biogenesis pathways may contribute to the development of PE.

Potential risk factors for hypospadias and negative correlation with DICER1 (rs3742330) A>G variant in Algerian population: A case-control study.

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. 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. 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. 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.

The 3' UTR polymorphisms rs3742330 in DICER1 and rs10719 in DROSHA genes are not associated with primary open-angle and angle-closure glaucoma: As case-control study.

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. 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). 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. 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.

Polymorphism rs3742330 in microRNA Biogenesis Gene DICER1 Is Associated with Pseudoexfoliation Glaucoma in Saudi Cohort.

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.

DROSHA rs10719 and DICER1 rs3742330 polymorphisms in endometriosis and different diseases: Case-control and review studies.

ObjectiveDROSHA 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. MethodsA 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. ResultsDICER1 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. ConclusionsThe 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.

Individual and joint effects of genetic polymorphisms in microRNA-machinery genes on congenital heart disease susceptibility.

Single-nucleotide polymorphisms in miRNA-machinery genes may alter the biogenesis of miRNAs affecting disease susceptibility. In this case-control study, we aimed to evaluate the impact of three single-nucleotide polymorphisms (DICER rs1057035, DROSHA rs10719, and XPO5 rs11077) and their combined effect in a genetic risk score model on congenital heart disease (CHD) risk. A total of 639 participants was recruited, including 125 patients with CHD (65 males; age 9.2 ± 10 years) and 514 healthy controls (289 males; age 15.8 ± 18 years). Genotyping of polymorphisms in miRNA-machinery genes was performed using a TaqMan®SNP genotyping assay. A genetic risk score was calculated by summing the number of risk alleles of selected single-nucleotide polymorphisms. There was a significantly increased risk of CHD in patients with XPO5 rs11077 CC genotype as compared to AC heterozygote and AA homozygote patients (ORadjusted = 1.7; 95% CI: 1.1-2.8; p = 0.018). A clear tendency to significance was also found for DROSHA rs10719 AA genotype and CHD risk for both codominant and recessive models (ORadjusted = 1.8; 95% CI: 0.91-3.8; p = 0.09 and ORadjusted = 1.9; 95% CI: 0.92-4; p = 0.08, respectively). The resulting genetic risk score predicted a 1.73 risk for CHD per risk allele (95% CI: 1.2-2.5; p = 0.002). Subjects in the top tertile of genetic risk score were estimated to have more than three-fold increased risk of CHD compared with those in the bottom tertile (ORadjusted = 3.52; 95% CI: 1.4-9; p = 0.009). Our findings show that the genetic variants in miRNA-machinery genes might participate in the development of CHD.

Genetic polymorphisms of miRNA machinery genes in bicuspid aortic valve and associated aortopathy.

Aim: SNPs in miRNA machinery genes may affect miRNA function by impacting their biogenesis. Here, we investigated the association between three SNPs in miRNA machinery genes (DICER rs1057035, DROSHA rs10719 and XPO5 rs11077) and bicuspid aortic valve (BAV). Materials & methods: Three polymorphisms were analyzed in 177 BAV patients and 414 healthy subjects by using a TaqMan®SNP assay. Results: The frequencies of XPO5 rs11077 genotype were significantly different between BAV patients and controls (p=0.022). On multivariate logistic regression analysis, the XPO5 rs11077 C allele resulted a significant predictor of BAV (odds ratioadjusted=0.65; CI: 0.42-0.98; p=0.047). Conclusion: The XPO5 rs11077 SNP was associated with a decreased BAV risk supporting the causative role of miRNAs in aortic valve development.

Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end-stage renal disease.

BackgroundMicroRNA (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).MethodA 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.ResultsCarrying 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].ConclusionVariants 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.

The effects of DICER1 and DROSHA polymorphisms on susceptibility to recurrent spontaneous abortion.

BackgroundRecurrent spontaneous abortion (RSA) is a serious problem in pregnancy. The exact etiology of RSA is unknown in more than 50% of all the patients. However, genetic variations are known as susceptibility factors for idiopathic RSA. Considering the role of miRNA biosynthesis machinery in the miRNA production and effect of miRNAs on various diseases, this study aimed to evaluate the effects of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms on RSA risk.MethodsIn this case‐control study, 150 RSA patients and 195 age‐matched healthy female controls were recruited. Both polymorphisms were genotyped using PCR‐RFLP method.ResultsThe frequency of DICER1 rs3742330AG genotype was higher in the control group (P = .022). There was a statistically significant association between rs3742330 polymorphism and a reduced RSA risk in dominant and allelic models (P = .013 and P = .007, respectively). No statistically significant association was found between DROSHA rs6877842 variant and RSA risk. The combination of AG and GC genotypes and G‐G alleles of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms led to a decreased RSA risk. However, the synergic effect of rs3742330A and rs6877842G alleles (A‐G) and AA‐GG genotypes was associated with an increased RSA risk.Conclusionthe DICER1 rs3742330AG genotype and combination of AG and GC genotypes and G‐G alleles of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms were associated with a reduced RSA risk.

Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population.

Objective: To evaluate the potential association between the genetic variants in miRNA processing genes (RAN, XPO5, DICER1, and TARBP2) and susceptibility to type 2 diabetes mellitus (T2DM) and its vascular complications, as well as to further investigate their interaction with environmental factors in type 2 diabetes.Methods: We conducted a case-control study in genotyping of five polymorphic loci, including RAN rs14035, XPO5 rs11077, DICER1 rs13078, DICER1 rs3742330, and TARBP2 rs784567, in miRNA processing genes to explore the risk factors for T2DM and diabetic vascular complications. Haplotype analyses, interactions of gene-gene and interactions of gene-environment were performed too.Results: We identified a 36% decreased risk of developing T2DM in individuals with the minor A allele in DICER1 rs13078 (OR: 0.64; 95%CI: 0.42–0.95; P: 0.026). The AA haplotype in DICER1 was also associated with a protective effect on T2DM compared with the AT haplotype (OR: 0.63; 95%CI: 0.42–0.94; P-value: 0.023). T2DM patients with the TT+TC genotype at RAN rs14035 had a 1.89-fold higher risk of developing macrovascular complications than patients with the CC genotype (OR: 1.89; 95%CI: 1.04–3.45; P-value: 0.037). We also identified two three-factor interaction models. One is a three-factor [DICER1 rs13078, body mass index (BMI), and triglyceride (TG)] interaction model for T2DM (OR: 5.93; 95%CI: 1.25–28.26; P = 0.025). Another three-factor [RAN rs14035, hypertension (HP), and duration of T2DM (DOD)] interaction model was found for macrovascular complications of T2DM (OR = 41.60, 95%CI = 11.75–147.35, P < 0.001).Conclusion: Our study provides new evidence that two single nucleotide polymorphisms (SNPs) of the miRNA processing genes, DICER1 and RAN, and their interactions with certain environmental factors might contribute to the risk of T2DM and its vascular complications in the southern Chinese population.

Association between Genetic Polymorphisms in microRNA Machinery Genes and Risk of Papillary Thyroid Carcinoma.

Evidence suggests that the microRNAs are involved in tumorigenesis and progression of various types of malignant tumors. Therefore, the aim of current research was to examine association between genetic variants in the miRNA machinery genes and risk of papillary thyroid carcinoma(PTC) in Iranian population. Peripheral blood samples were collected from 120 PTC patients and 130 healthy subjects. Genotyping of polymorphisms in miRNA Machinery genes (DICER1 rs3742330, DROSHA rs6877842 and XPO5 rs11077) polymorphisms was performed using PCR-RFLP method. Chi square and independent sample t tests were applied for categorical and continuous variables, respectively. In this study, we found that frequency of DICER1 rs3742330G allele was significantly higher in controls compared to PTC patients. In addition, the DICER1 rs3742330 polymorphism was associated with lower risk of PTC in dominant (AG + GG vs. AA, OR = 0.5, 95%CI = 0.3-0.9, P = 0.03) model. No association was found between DROSHA rs6877842 and XPO5 rs11077 polymorphisms and PTC neither in dominant nor in recessive and allelic models. The frequency of DROSHA rs6877842GC genotype was higher in PTC patients with smaller tumor size (<1). Therefore, this polymorphism could be a protective factor for tumor development in PTC patients (OR = 0.3, 95%CI = 0.1-1, P = 0. 04). The current study indicated that DICER1 rs3742330 polymorphism was associated with lower risk of PTC. Furthermore, DROSHA rs6877842 polymorphism could be a protective factor for tumor development in PTC patients.

Dietary Lutein Plus Zeaxanthin Intake and DICER1 rs3742330 A\u2009>\u2009G Polymorphism Relative to Colorectal Cancer Risk

It is unclear whether dietary lutein/zeaxanthin intake in colorectal cancer is associated with microRNA processing involved in DICER1 cleavage for messenger RNA translation. We investigated whether dietary lutein/zeaxanthin intake affects colorectal cancer risk in patients with a DICER1 rs3742330 polymorphism. In this hospital-based case-control study, we recruited 923 colorectal cancer patients and 1,846 controls based on eligibility criteria, a semiquantitative food frequency questionnaire and the DICER1 rs3742330 genotype. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for confounders. The highest quartile of lutein/zeaxanthin consumption was inversely associated with a reduced colorectal cancer risk (OR, 95% CI = 0.25, 0.18–0.36). Carrying G allele (AG + GG) showed a significantly reduced colorectal cancer incidence compared with that of AA carriers (OR, 95% CI = 0.71, 0.55–0.91). Those carrying the G allele (AG + GG) along with high lutein/zeaxanthin consumption were markedly associated with a decreased colorectal cancer risk (OR, 95% CI = 0.32, 0.22–0.46, P for interaction = 0.018), particularly for rectal cancer (OR, 95% CI = 0.24, 0.15–0.39, P for interaction = 0.004), compared with that of AA carriers with low lutein/zeaxanthin intakes. In conclusion, colorectal cancer risk was related to an interactive effect between dietary lutein/zeaxanthin intake and the DICER1 rs3742330 polymorphism.

Association of variants of miRNA processing genes with cervical precancerous lesion risk in a southern Chinese population.

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), including Ran-GTP (RAN) rs14035, exportin-5 (XPO5) rs11077, DICER1 rs3742330, DICER1 rs13078, and TARBP2 rs784567, were genotyped in a case–control study to estimate risk factors of cervical precancerous lesions. The gene–environment interactions and haplotype association were estimated. We identified a 27% decreased risk of cervical precancerous lesions for individuals with minor G allele in DICER1 rs3742330 (odds ratio (OR) = 0.73, 95% confidence interval (95% CI) = 0.58–0.92, P = 0.009). The AG and AG/GG genotypes in DICER1 rs3742330 were also found to decrease the risk of cervical precancerous lesions (AG compared with AA: OR = 0.51, 95% CI = 0.35–0.73, P <0.001; AG/GG compared with AA: OR = 0.54, 95% CI = 0.39–0.77, P = 0.001). The GT haplotype in DICER1 had a risk effect on cervical precancerous lesions compared with the AT haplotype (OR = 1.36, 95% CI = 1.08–1.73, P = 0.010). A two-factor (DICER1 rs3742330 and human papillomavirus (HPV) infection) and two three-factor (model 1: rs3742330, passive smoking, and HPV infection; model 2: rs3742330, abortion history, and HPV infection) interaction models for cervical precancerous lesions were identified. In conclusion, the genetic variants in the miRNA processing genes and interactions with certain environmental factors might contribute to the risk of cervical precancerous lesions in southern Chinese women.

Genetic variants in miRNA machinery genes associated with clinicopathological characteristics and outcomes of gastric cancer patients.

Polymorphisms in miRNA machinery genes have been proved to be related to risk or survival of several kinds of cancers, but the results are controversial and the role of these polymorphisms in gastric cancer remains uncertain. In our study, we investigated the association between five genetic variants in miRNA machinery genes ( DICER, RAN, XPO5 [name of the gene]) and clinical outcomes in Chinese gastric cancer patients. A total of 96 patients with stage IB-III gastric cancer treated with radical gastrectomy and adjuvant chemotherapy of oxaliplatin and fluorouracils were analyzed. The MassARRAY MALDI-TOF system was used to determine the genotypes. DICER rs3742330 AG+GG genotype was associated with more advanced T stage compared to AA genotype ( P=0.009). More patients with XPO5 rs2257082 CC genotype had poorly differentiated tumors compared with CT+TT genotype carriers. After adjustment by age, sex, differentiation, T stage, and lymph node status, XPO5 rs2257082 CC genotype carriers were found to have worse disease-free survival than CT+TT genotype carriers (adjusted HR 3.099; 95% CI 1.270, 7.564; P=0.013), carriers of RAN rs14035 CC genotype had higher three-year OS rate than carriers of CT+TT genotype (adjusted HR 3.174; 95% CI 1.010, 9.973; P=0.048). These results indicated that genetic variants in miRNA machinery genes might be associated with the clinicopathological features and prognosis of completely resected gastric cancer patients.

Relationships between Dicer 1 polymorphism and expression levels in the etiopathogenesis of preeclampsia.

Preeclampsia (PE) is a pregnancy-specific complication which is a major cause of maternal and fetal morbidity and mortality. Recent studies have shown the aberrant expression of microRNAs (miRNAs) in the placenta of patients with PE. Dicer1 is a key enzyme in the generation of small noncoding RNAs including miRNAs. The aim of this study is to investigate the relationship between maternal and placental Dicer1 rs3742330 polymorphism and placental Dicer1 mRNA expression in PE and normotensive pregnant women. The blood and placenta of PE pregnant and normotensive pregnant women were collected after delivery. Dicer1 rs3742330 polymorphism was genotyped using PCR-RFLP method. The mRNA expression levels were measured using quantitative real time PCR. The maternal Dicer1 rs3742330 polymorphism was not associated with PE or PE severity; however, the placental Dicer1 rs3742330 AG genotype was associated with two fold higher risk of PE and three fold higher risk of severe PE (P = 0.018 and P = 0.005, respectively). The relative mRNA expression of Dicer1 gene in the placenta did not differ between the two groups. In addition, the relative mRNA expression of Dicer1 gene was significantly lower in the placenta of women with rs3742330 AG+GG genotypes in the total population (P = 0.028) and PE women (P = 0.004), but not in the control group. In conclusion, there was a relationship between placental but not maternal Dicer1 rs3742330 polymorphism and PE. There was no difference in Dicer1 mRNA expression between the PE and control groups; however, it was significantly lower in the placenta of women with rs3742330 AG+GG genotypes.

Genetic variants in the microRNA machinery gene (Dicer) have a prognostic value in the management of endometrial cancer.

Although several associations were found between Dicer rs3742330 single nucleotide polymorphism (SNP) and development and prognosis of some epithelial cancers, relationship between the SNP rs3742330 and endometrial cancer (EC) has not yet been studied. We aimed to investigate the prognostic role of rs3742330 SNP of Dicer gene in EC patients. A total of 80 EC patients and 80 control subjects included in the study. Real-time polymerase chain reaction and the allele discrimination technique was used for genotyping of rs3742330 SNP. There was no significant difference between EC patients and control subjects with regard to the genotype and allele frequencies for Dicer rs3742330 SNP (P > 0.05). Despite Dicer rs3742330 SNP had no prognostic value in terms of stage, grade, lymphovascular invasion, myometrial invasion, tumor size, and histopathology; malignant peritoneal cytology has been detected higher in the patients bearing AA genotype compare with AG genotype (P = 0.023). Higher recurrence rate and shorter time to recurrence were found in patients bearing AG and GG genotype compare with AA genotype (P = 0.009). Dicer rs3742330 AG and GG genotypes may have the potential to be used as a predictor of poor prognosis in the management of EC case.

Association of rs1057035polymorphism in microRNA biogenesis pathway gene (DICER1) with azoospermia among Iranian population.

Since genes involved in microRNA biogenesis pathways have a main role in impaired spermatogenesis, in this research, we evaluated different genotypes frequency of seven single-nucleotide polymorphisms in DICER1 and DROSHA genes. Different genotypes frequency of DICER1 (rs12323635, rs1057035, rs13078 and rs3742330) and DROSHA (rs10719, rs642321 and rs2291102) were determined by sequencing method in 385 infertile men and 120 fertile controls. It was found that CC genotype (P = 0.000) and C allele (P = 0.0) of rs1057035 T > C polymorphism were associated with idiopathic male infertility (azoospermia). Gene expression study in blood and testis samples was done by real time PCR technique. Our results showed significant under expression of DICER1 gene in blood and testis tissues of azoospermic samples (P < 0.05), but we did not observed significant difference in expression ratio between infertile men with and without C allele of rs1057035 SNP (P > 0.05). The results of this study showed that among the studied variants, only one of them in DICER1 might be associated with azoospermia, but additional studies needs in different populations and ethnics.

Genetic variant in DICER gene is associated with prognosis of hepatocellular carcinoma in a Chinese cohort.

MicroRNAs (miRNAs) function as gene regulators and play crucial roles in the pathogenesis and prognosis of hepatocellular carcinoma (HCC). Genetic variants in miRNA processing genes may affect miRNA expression and contribute to HCC risk and survival. We hypothesized that single nucleotide polymorphisms (SNPs) in miRNA processing genes may be associated with HCC susceptibility and prognosis. The study aims to verify whether this hypothesis is right or not. We first genotyped the selected three SNPs in miRNA processing genes (RAN rs3803012 A>G, HIWI rs10773771 T>C, and DICER rs1057035 T>C) in 312 HCC patients and 320 cancer-free controls using the TaqMan assay, and evaluated the associations of the three SNPs with HCC risk. We also investigated the effect of the three SNPs on the overall survival of 312 HCC patients. There were no significant associations between the three SNPs (RAN rs3803012 A>G, HIWI rs10773771 T>C, and DICER rs1057035 T>C) and HCC risk. However, HCC patients carrying DICER rs1057035 CT + CC genotypes had significantly longer median survival time (log-rank, P = 0.018) and decreased death risk (adjusted hazard ratio = 0.68; 95% confidence interval, 0.49-0.95; P = 0.022) than patients with rs1057035 TT genotypes. The DICER rs1057035 genotype was an independent protective factor for HCC survival (CT + CC vs. TT: hazard ratio = 0.72; 95% confidence interval,0.55-0.96; P = 0.031). This study provides evidence that DICER rs1057035 T>C polymorphism may be a prognostic biomarker for HCC patients.

DICER and DROSHA gene expression and polymorphisms in autoimmune thyroid diseases

Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotyped DICER rs3742330A/G and rs1057035T/C as well as DROSHA rs644236C/T and rs10719C/T polymorphisms in 255 Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method. We also examined the expression of DICER and DROSHA gene in peripheral blood mononuclear cells (PBMCs) by quantitative RT-PCR (qRT-PCR) methods. The TT genotype of the DICER rs1057035 polymorphism was less frequent in GD patients (p = 0.0098) than in healthy subjects. The CC genotype of DROSHA rs644236 polymorphism were more frequent in GD patients than in HD patients (p = 0.0171). The gene expression of DICER was lower in patients with AITD compared with that in control subjects (p = 0.0064) and was lower in patients with GD in remission than in patients with intractable GD (p = 0.0213). In addition, the expression of DROSHA was lower in patients with AITD than that in control subjects (p < 0.0001) and was lower in patients with severe HD than in patients with mild HD (p = 0.0440). In conclusion, the DICER rs1057035 TT genotype and DROSHA rs644236 CC genotype were associated with the development of GD and the differentiation between GD and HD, respectively. The expression levels of DICER and DROSHA genes were low in AITD and differed depending on the intractability of GD and the severity of HD, respectively.