RESUMEN

The effect of DNA methylation on gene expression triggered it as a susceptibility factor in various diseases including preeclampsia (PE). The pathogenesis of PE is closely associated with the methylation status and genetic variants of relevant genes. Therefore, the aim of the study was to investigate the possible impacts of the placental DNA methylation and rs3741219, rs217727, and rs2107425 polymorphisms of the H19 gene on the PE susceptibility as well as the its mRNA expression. Moreover, eight haplotypes of three loci in the H19 gene were analyzed. In this case-control study, the placentas of 107 preeclamptic and 113 non-preeclamptic women were collected after delivery. The methylation status was assessed by methylation-specific polymerase chain reaction (PCR). The H19 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism or amplification refractory mutation system-polymerase chain reaction methods. The quantitative real time PCR was used for mRNA expression assay. The placental H19 rs3741219 and rs2107425 polymorphisms were not associated with PE. However, H19 rs217727CT and TT genotypes might be associated with a 9.2- and 17.7-fold increased risk of PE, respectively. The Trs3741219 Crs217727 Crs2107425 and Trs3741219 Crs217727 Trs2107425 haplotypes were significantly lower, whereas the Trs3741219 Trs217727 Crs2107425 and Crs3741219 Trs217727 Crs2107425 haplotypes were significantly higher in PE women. Promoter but not upstream region hypermethylation of H19 gene could be led to decreased risk of PE (MM vs. UM + UU). No significant difference was observed in the placental mRNA expression between two groups. The H19 expression was significantly higher in women with unmethylated (UU), compared to methylated promoter (MM). The H19 expression was 17- and 15-fold higher in H19-rs2107425 CC and CT genotypes in PE women. In conclusion, the H19 rs2107425 polymorphism was associated with a higher risk of PE and increased H19 mRNA expression. The promoter hypermethylation of H19 gene was associated with a lower risk of PE and decreased H19 mRNA expression.

Asunto(s)

Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Regiones Promotoras Genéticas , ARN Largo no Codificante/genética , Adulto , Estudios de Casos y Controles , Metilación de ADN , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Desequilibrio de Ligamiento , Edad Materna , Placenta/fisiología , Embarazo , ARN Mensajero/genética

RESUMEN

Purpose: Vitamin D deficiency may be a main causative agent in the pathogenesis of preeclampsia (PE). The actions of the active form of vitamin D are mediated via the vitamin D receptor (VDR), which is expressed in numerous organs including placenta. Therefore, we evaluated the potential relationship between maternal and placental VDR polymorphisms and the predisposition to PE in an Iranian population.Methods: This case-control study surveyed 152 PE and 160 normotensive pregnant women. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal and placental VDR Fok1 rs2228570, Bsm1 rs1544410, Taq1 rs731236, and Apa1 rs7975232 polymorphisms.Results: The maternal but not placental VDR FokI Ff genotype, was significantly lower in PE women (P = .02 and P = .06, respectively). The maternal and placental VDR FokI polymorphism was associated with lower PE risk in the dominant model (Ff+ff vs. FF) and these genotypes could decrease PE risk (OR, 0.5 [95% CI, 0.3-0.8], P = .007 and OR, 0.5 [95% CI, 0.3-0.9], P = .02, respectively). The haplotype analysis revealed that the maternal and placental TABf haplotype may lead to decreased risk of PE. In addition, the placental TABF haplotype was associated with higher risk of PE. No relationship was observed between PE susceptibility and the maternal and placental VDR Bsm1, Taq1 and Apa1 polymorphisms. There was also no relationship between the maternal and placental VDR polymorphisms and PE severity.Conclusions: the maternal and placental VDR FokI variant was associated with decreased risk of PE in the dominant model.

Asunto(s)

Polimorfismo Genético/genética , Preeclampsia/genética , Receptores de Calcitriol/genética , Adulto , Estudios de Casos y Controles , Familia , Femenino , Genotipo , Haplotipos/genética , Humanos , Irán , Placenta , Reacción en Cadena de la Polimerasa , Embarazo , Factores de Riesgo , Vitamina D/fisiología , Deficiencia de Vitamina D/genética

RESUMEN

BACKGROUND: Preeclampsia (PE), as a multisystem disorder, is associated with maternal hypertension and proteinuria. Apoptosis seems to be involved in the pathophysiology of PE, although its precise pathogenic mechanisms are not well established. In this study, we aimed to identify the association between maternal TP53-rs1042522, P21-rs1801270, and P21-rs1059234 polymorphisms and PE. In addition, we examined the effects of promoter methylation and TP53 and P21 polymorphisms on placental mRNA expression in PE women. METHODS: The blood of 226 PE women and 228 normotensive pregnant women was examined in this study. In addition, the placentas were genotyped in 109 PE and 112 control women. The methylation status was assessed by a methylation-specific PCR assay, while mRNA expression was examined via Quantitative Real Time PCR. RESULTS: The maternal and placental P21-rs1801270 CA genotype had a significant association with the reduced risk of PE. In the dominant, recessive, and allelic models, maternal/placental P21-rs1059234 polymorphism had no statistically significant association with the risk of PE. On the other hand, the reduced risk of PE was associated with maternal, but not placental TP53-rs1042522 polymorphism in the dominant and recessive models. The maternal and placental P21-rs1801270 polymorphism was associated with PE risk. The maternal P21 Trs1059234Crs1801270 haplotype was associated with 3.4-fold increase in PE risk, However the maternal P21 Trs1059234Ars 1801270 haplotype and placental Crs1059234CA rs1801270 haplotype led to 0.5 and 0.4-fold decrease in PE risk, respectively. PE women showed 5.6 times higher levels of placental mRNA expression of TP53 gene, although it was not associated with rs1042522 polymorphism. The relative placental mRNA expression of P21 gene was 0.2 in PE women. It was also 2.4 times higher in individuals with rs1801270CA genotype than those with AA genotype. The hyper-methylation of P21 and TP53 genes in the promoter region was associated with a 3.4-fold and 3-fold increase in PE risk, respectively. However, no association was found between P21 and TP53 mRNA expression and promoter methylation. CONCLUSION: In conclusion, P21-rs1801270 and TP53-rs1042522 polymorphisms were involved in reduced risk of PE. P21-rs1801270 was associated with decreased P21 mRNA expression. The hyper-methylation of P21 and TP53 genes in the promoter region was associated with a higher PE risk.

Asunto(s)

Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Metilación de ADN , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Transcriptoma , Proteína p53 Supresora de Tumor/genética , Adulto , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Femenino , Humanos , Placenta/metabolismo , Embarazo , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto Joven

RESUMEN

Objective: Uterine leiomyoma (UL) can be considered as the most common benign gynecological tumors of the smooth muscle cells in the myometrium. They are likely to be associated with infertility and recurrent abortion as well as obstructed labor and post-partum hemorrhage. Moreover, altered vascular-related genes can be linked to developing leiomyoma. Polymorphisms of the angiotensin-converting enzyme (ACE) gene are associated with some vascular diseases. The present study was carried out to investigate the association of ACE I/D and AGTR1 A1166C gene polymorphisms and the risk of uterine leiomyoma in a sample of Iranian population. Methods: The study was carried out on a total of 413 women divided into 202 patients with diagnosed uterine leiomyomas and a control group of 211. Genotyping was performed using the PCR or PCR-RFLP methods. Results: The ID and DD genotypes of ACE I/D polymorphism were associated with 2 and 2.9 fold higher risk of UL compared to II genotype (OR, 2 [95% CI, 1.3 to 3.2]; P = 0.004 and OR, 2.9 [95% CI, 1.6 to 5]; P = 0.0002). The frequencies of ACE D alleles were 53.7% in women with UL and 40.3% in controls, which were observed to be statistically different (P < 0.0001). The alleles and genotypes of AGTR1 A1166C polymorphism were not different between UL and control women (P=0.9). Conclusion: The ACE ID and DD genotypes were associated with a higher risk of UL. No relationship was found between AGTR1 A1166C polymorphism and UL.

Asunto(s)

Predisposición Genética a la Enfermedad , Leiomioma/etiología , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Receptor de Angiotensina Tipo 1/genética , Neoplasias Uterinas/etiología , Adulto , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Leiomioma/patología , Pronóstico , Factores de Riesgo , Neoplasias Uterinas/patología

RESUMEN

Preeclampsia (PE) is a serious pregnancy complication whose etiology is not fully understood. However, previous reports have suggested that oxidative stress and genetic variants may contribute to the development of PE. This study aimed to examine the relationship between the Glutathione peroxidase-1(GPx-1) and Manganese Superoxide dismutase (MnSOD) polymorphisms and preeclampsia (PE) risk in Iranian women. Genotyping of the studied women, including 179 preeclamptic cases and 202 controls, for GPx-1 rs1050450 and MnSOD rs4880 polymorphisms was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our results showed a 1.7- to 1.6-fold increased risk of PE in the rs1050450 CT and CT + TT (dominant model) genotypes compared to CC genotype (OR = 1.7, 95%CI 1.1-2.7; P = 0.01 and OR = 1.6, 95%CI 1.1-2.4; P = 0.02; respectively). We also found a marked correlation between TC and CC genotypes of MnSOD rs4880 polymorphism and a 1.9- to 2.3-fold increase risk of PE (OR = 1.9, 95%CI 1.2-2.9; P = 0.005 and OR = 2.3, 95%CI 1-5.1; P = 0.04, respectively). The rs4880 MnSOD polymorphism was correlated with increased risk of PE in the allelic and dominant models (OR = 1.8, 95% CI 1.2-2.5, P = 0.002; OR = 1.9, 95%CI 1.3-3, P = 0.002, respectively). High frequency of TC/CC genotype of MnSOD rs4880 and CT genotypes of rs1050450 polymorphism in PE patients compared to controls showed the contribution of these variants to PE susceptibility.

Asunto(s)

Alelos , Predisposición Genética a la Enfermedad , Glutatión Peroxidasa/genética , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Superóxido Dismutasa/genética , Biomarcadores , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Oportunidad Relativa , Estrés Oxidativo , Preeclampsia/diagnóstico , Preeclampsia/metabolismo , Embarazo , Factores de Riesgo , Glutatión Peroxidasa GPX1

RESUMEN

Preeclampsia (PE) is a gestational disorder and genetic and epigenetic alterations can affect its pathogenesis. Some evidences showed that the altered expression of miRNAs in the placentas complicated by PE. The blood samples from 219 PE and 242 normotensive pregnant women and placental tissue samples from 111 PE and 119 normotensive women were collected. MiR-146a and miR-149 polymorphisms were genotyped in blood samples and placentas using PCR-RFLP method. The frequencies of maternal miR-146a rs2910164 GC and CC genotypes did not differ between PE and control groups. However, the miR-146a rs2910164 G/C polymorphism was associated with an increased risk of PE in dominant (OR 1.5, 95% CI 1-2.1; P = 0.04) and allelic (OR 1.4, 95% CI 1-1.9; P = 0.04) but not recessive models. Moreover, the maternal GC and CC genotypes were associated with a 1.9- and 3.4-fold increased risk of severe PE (OR 1.9, 95% CI 1.1-3.2; P = 0.02 and OR 3.4, 95% CI 1.3-9; P = 0.01, respectively) and miR-146a rs2910164 polymorphism could increase risk of severe PE in dominant and recessive models (OR 2.1, 95% CI 1.3-3.4; P = 0.004 and OR 2.6, 95% CI 1-6.7; P = 0.04). The placental miR-146a rs2910164 polymorphism was associated with PE susceptibility in dominant (OR 1.8, 95% CI 1.1-3; P = 0.03) and allelic models (OR 1.7, 95% CI 1.1-2.5; P = 0.02). The frequencies of maternal and placental miR-149 rs2292832 genotypes were not different between two groups and these genotypes were not associated with PE or severe PE risk. In conclusion, according to logistic regression analysis the maternal/placental miR-146a rs2910164 G/C polymorphism was associated with PE and/or severe PE risk.

Asunto(s)

MicroARNs/genética , Preeclampsia/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , MicroARNs/metabolismo , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Preeclampsia/metabolismo , Embarazo

RESUMEN

HOX transcript antisense RNA (HOTAIR) as a lncRNA involves in epigenetic regulation of various genes. Several studies have been suggested the effects of HOTAIR polymorphisms on different diseases. The aim of the present study was to evaluate the effect of maternal and placental HOTAIR polymorphisms on risk of preeclampsia (PE). The maternal blood of 203 preeclamptic and 202 nonpreeclamptic pregnant women as well as the placentas of 87 of preeclamptic and 95 nonpreeclamptic pregnant women were genotyped for HOTAIR polymorphisms. There was no association between maternal and placental HOTAIR polymorphisms (rs12826786, rs920778, and rs1899663) and PE risk. However, the maternal rs4759314AG and dominant model genotypes were associated with increased risk of PE. The maternal and placental HOTAIR rs10783618 polymorphism was associated with PE risk in recessive and allelic models. Haplotype analysis showed that, the maternal CTGAT and CCTAT and placental CTGAT haplotypes were significantly higher and maternal CTGAC, TCTAT, and TTGAT and placental CTGAC haplotypes were significantly lower in PE women. In silico analysis revealed that HOTAIR rs1899663 had a main effect on the secondary structure of mRNA, however, HOTAIR rs4759314 variant had potential alteration of splicing. In conclusion, the maternal and placental HOTAIR rs10783618 polymorphism might increase PE susceptibility. © 2019 IUBMB Life, 71(9):1367-1381, 2019.

Asunto(s)

Predisposición Genética a la Enfermedad , Conformación de Ácido Nucleico , Preeclampsia/genética , ARN Largo no Codificante/genética , Adulto , Alelos , Simulación por Computador , Epigénesis Genética/genética , Femenino , Estudios de Asociación Genética , Genotipo , Haplotipos/genética , Humanos , Placenta , Polimorfismo de Nucleótido Simple/genética , Preeclampsia/patología , Embarazo , ARN Mensajero/química , ARN Mensajero/genética

RESUMEN

Uterine leiomyoma (UL) is the most common benign tumor of the uterus. HOX transcript antisense RNA (HOTAIR) as a lncRNAs is the product of HOXC gene that plays a major role in the invasion and development of different tumors. Several lines of evidence have been suggested the effects of HOTAIR polymorphisms on cancer risk. The aim of the present study was to analyze the effects of HOTAIR polymorphisms (rs12826786, rs920778, rs4759314 and rs1899663) on UL in southeast of Iran. A total of 152 women with UL and 182 age-matched healthy women were selected in the case-control study. The PCR-RFLP and ARMS-PCR methods were used for genotyping. HOTAIR rs920778 polymorphism was associated with a lower risk of UL in dominant [OR, 0.5 (95% CI, 0.3-0.9); P = 0.03], recessive [OR, 0.6 (95% CI, 0.4-0.9; P = 0.016] and allelic models [OR, 0.6(95% CI, 0.5-0.9); P = 0.004]. However, HOTAIR rs12826786 polymorphism was associated with a higher risk of UL in dominant [OR, 2.6 (95% CI, 1.6-4.1); P = 0.0001], recessive [OR, 1.9 (95% CI, 1-3.6); P = 0.04] and allelic models [OR, 1.8 (95% CI, 1.3-2.4); P = 0.0003]. There was no association between HOTAIR rs4759314 and rs1899663 polymorphisms and UL susceptibility. The frequency of CTGA haplotype was lower in UL women; however, the CCGA, TCGA, TTTA, and TTGA haplotypes were more frequent in UL women. Our results indicated that HOTAIR rs12826786 and rs920778 polymorphisms had a significant effect on UL susceptibility. The HOTAIR haplotypes could affect UL susceptibility.

Asunto(s)

Leiomioma/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos , Proteínas de Homeodominio/genética , Humanos , Irán , Leiomioma/metabolismo , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo

RESUMEN

Evidence showed that, pro inflammatory cytokines and mediators of innate immune responses may involve in the pathogenesis of preeclampsia (PE). Therefore, the present investigation aimed to examine the possible effects of placental TNF-α and TLR4 polymorphisms on PE susceptibility. METHODS: The placental tissues were collected after delivery from 111 PE and 115 healthy pregnant women. The TNF-α-308G/A (rs1800629), TNF-α-238G/A (rs361525), TLR4 Asp299Gly (rs4986790) and TLR4 Thr399Ile (rs4986791) polymorphisms were genotyped using PCR-RFLP method. Moreover, in-silico analysis was performed to evaluate the potential functions of these polymorphisms. RESULTS: The TNF-α -308 GA genotype was associated with a decreased PE risk. The frequency of TNF-α -238G/A genotypes did not differ between two groups, however, the frequency of TNF-α -238A allele was significantly higher in controls. No relationship between TLR4 Thr399Ile and Asp299Gly polymorphisms and PE was found. In-silico analysis predicted that -308G to A substitution in the TNF-α promoter might lead to different allelic expressions. In addition, TLR4 Asp299Gly polymorphism would result in a major change in the mRNA and protein functions. CONCLUSION: Our study for the first time presented evidence on the association of the placental TNF-α -308GA genotype and TNF-α -238A allele with decreased risk of PE in an Iranian population.

Asunto(s)

Predisposición Genética a la Enfermedad , Placenta/metabolismo , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Preeclampsia/fisiopatología , Receptor Toll-Like 4/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Alelos , Sitios de Unión , Biología Computacional/métodos , Citocinas/metabolismo , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Haplotipos , Humanos , Mediadores de Inflamación/metabolismo , Modelos Moleculares , Conformación de Ácido Nucleico , Oportunidad Relativa , Preeclampsia/metabolismo , Embarazo , Unión Proteica , Relación Estructura-Actividad , Receptor Toll-Like 4/química , Factor de Necrosis Tumoral alfa/química , Adulto Joven

RESUMEN

The current study examined the effects of BAX and BCL2 polymorphisms and methylation as well as mRNA expression on susceptibility to PE. After delivery, the placentas were collected from 92 women with PE, as well as 106 normotensive pregnant women. The BAX rs4645878 and BCL2 rs2279115 polymorphisms were genotyped by the PCR-RFLP method. Methylation-specific PCR (MSP) was used for analysis of promoter methylation. mRNA expression was assayed by Quantitative RT-PCR. In addition, in silico analysis was performed by bioinformatics tools. There was no relationship between PE and placental BAX rs4645878 and BCL2 rs2279115 polymorphisms. The groups were not significantly different regarding the promoter methylation of BAX gene. Nonetheless, the MM status of BCL2 promoter had a significantly higher frequency in the PE group and was associated with 2.7-fold higher risk of PE (OR = 2.7, 95% CI = 1.3-5.6; P = 0.01). The relative mRNA expression of BCL2 was decreased in the placentas of PE women (P < 0.0001). The expression of BAX gene was not significantly different between the two groups. There was no association between placental BAX rs4645878 and BCL2 rs2279115 polymorphisms and mRNA expression levels. In silico analysis indicated that BAX rs4645878 and BCL2 rs2279115 polymorphisms were located in the core recognition site of different transcription factors and these substitutions of wild allele resulted in the loss and/ or change of these binding sites and subsequently may alter BCL2 and BAX expression. This study showed that the BAX and BCL2 polymorphisms and BAX promoter methylation were not associated with PE risk. The BCL2 promoter methylation was associated with lower BCL2 expression and higher PE susceptibility.

Asunto(s)

Epigénesis Genética/genética , Placenta/metabolismo , Polimorfismo de Nucleótido Simple/genética , Preeclampsia/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteína X Asociada a bcl-2/genética , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Embarazo , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética

RESUMEN

Evidence showed that microRNA biosynthesis plays the main role in pathogenesis of several diseases including Preeclampsia (PE). Therefore, microRNA processing enzymes may involve in PE predisposition. The aim of the present study was to evaluate the relation between DROSHA rs10719 and rs6877842 polymorphisms and mRNA expression in the placenta of PE women and controls. This study recruited 110 PE women and 115 age matched normotensive pregnant women for genotyping of DROSHA polymorphisms and analyzing of mRNA expression. There was no association between alleles and genotypes of placental DROSHA rs10719 and rs6877842 polymorphisms and PE susceptibility. However, placental DROSHA rs10719 was associated with increased PE risk in the recessive model. The combination of CC/GG genotypes of DROSHA rs10719 and rs6877842 polymorphisms was associated with higher risk of PE. The frequency of C-G haplotype was higher in PE women, but the difference was not significant. The DROSHA mRNA expression was downregulated in the placenta of PE women. There was no relation between DROSHA mRNA expression and rs6877842 polymorphism, however, it was decreased in the placenta of women with rs10719CC genotype. The placental DROSHA rs10719 but not rs6877842 polymorphism could be a risk factor for PE susceptibility only in the recessive model. The combination of CC/GG genotypes could be risk factors for PE susceptibility. The DROSHA expression downregulated in the preeclamptic placentas and those carrying rs10719CC genotype.

Asunto(s)

Presión Sanguínea/genética , Placenta/enzimología , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Ribonucleasa III/genética , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Heterocigoto , Homocigoto , Humanos , Fenotipo , Preeclampsia/diagnóstico , Preeclampsia/enzimología , Preeclampsia/fisiopatología , Embarazo , Medición de Riesgo , Factores de Riesgo , Adulto Joven

RESUMEN

BACKGROUND: Preeclampsia (PE) is one of the main causes of death among the pregnant women as well as newborns. Although the etiological cause of preeclampsia is not yet clear, a range of risk factors has been suggested. MicroRNAs (like miRNA-152) are small non-coding molecules that play a role in a wide spectrum of biological processes, such as cell proliferation and angiogenesis. This study aimed to investigate the possible relationship of miRNA-152 rs12940701 polymorphism and the risk of preeclampsia among the pregnant women as compared with the control group. METHODS: Genotyping of miRNA-152 rs12940701 polymorphism was performed using blood and placenta samples of 223 preeclampsia women and 229 normotensive pregnant women by a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The results obtained from maternal blood showed an increase in T alleles for PE women, that there was no significant difference between the PE and control group (OR = 1.7, P = 0.19). In addition, no significant difference was found in the TT genotype between the two groups (11.6% vs. 7%, OR = 1.4, P = 0.3). Similarly, the results obtained from placental samples were identical. CONCLUSIONS: A lack of relationship between the polymorphism of miRNA-152 rs12940701 gene and preeclampsia development has been shown.

Asunto(s)

MicroARNs/metabolismo , Polimorfismo Genético/genética , Preeclampsia/genética , Adulto , Femenino , Predisposición Genética a la Enfermedad , Humanos , Recién Nacido , Embarazo

RESUMEN

BACKGROUND: Preeclampsia (PE), is a pregnancy-specific complication with the placental origin which associated with altered expression of angiogenic factors. Vascular Endothelial Growth Factor (VEGF), is a growth and hypoxia-induced factor which contributes to the regulation of various processes. The present study has investigated the association of the placental VEGF -634G/C (rs2010963), -1154G/A (rs1570360), and -2549 I/D (18bpindel) polymorphisms in the promoter region with VEGF mRNA expression in PE women and control group. METHODS: This case-control study was performed on the placenta of 84 PE women and 103 controls after delivery. Genotyping of the VEGF polymorphisms was done by PCR or PCR, PCR-RFLP or sequencing methods. The mRNA expression levels were measured by Quantitative Real-Time PCR. RESULTS: The relative mRNA expression of VEGF gene was significantly higher in PE women compared to controls. The relative mRNA expression of VEGF gene was significantly higher in women with -634CC genotype compared to CG + GG genotypes in PE women and total studied women but not in control women. However, there was no association between the placental VEGF -1154G/A and -2549 I/D polymorphisms and VEGF mRNA expression neither in PE nor in control groups. CONCLUSION: The current study found higher mRNA expression of placental VEGF gene in PE women. The mRNA expression of the placental VEGF gene has been up-regulated in the placenta of women with -634CC genotype. No association was found between the placental VEGF -1154G/A and -2549 I/D polymorphisms and VEGF mRNA expression.

Asunto(s)

Placenta/metabolismo , Polimorfismo Genético/genética , Preeclampsia/metabolismo , Regiones Promotoras Genéticas/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Preeclampsia/genética , Embarazo , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba/genética , Factor A de Crecimiento Endotelial Vascular/genética

RESUMEN

MicroRNAs (miRNAs) are a class of noncoding small RNAs which regulate gene expression through post-transcriptional repression or degradation of messenger RNA. They play very important roles in various biological processes including growth, differentiation, and proliferation, as well as apoptosis, angiogenesis, and metabolism. Therefore, in the present study, we evaluated the possible effect of functional rs7372209C/T polymorphism in the 5'- region of pri-miRNA- 26a1gene on preeclampsia(PE) susceptibility. This case-control study was conducted on 219 PE women and 204 unrelated healthy controls. The amplification refractory mutation system-polymerase chain reaction method was used for rs7372209C/T genotyping. The pri-miRNA- 26a1 rs7372209CT genotype was associated with decreased PE risk (OR, 0.5 [95% CI, 0.3-0.8], P = 0.001). The frequency of rs7372209TT genotype did not differ between two groups. In addition, the pri-miRNA- 26a1 rs7372209 polymorphism was associated with lower risk of PE in dominant model (CT+TT vs CC) (OR, 0.5 [95% CI, 0.4-0.8], P = 0.002). Although there was no significant difference between mild and severe PE women according to rs7372209CT genotype, the differences between mild and severe PE groups with controls remained significant. The frequency of pri-miRNA-26a1 rs7372209CT genotype was not different between late-onset PE and early onset PE groups. The present study showed for the first time that the pri-miRNA- 26a1 rs7372209 polymorphism was associated with lower risk of mild and severe PE in the dominant model and this polymorphism could be a protective factor for PE susceptibility.

Asunto(s)

MicroARNs/genética , Polimorfismo Genético/genética , Preeclampsia/genética , Adulto , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Reacción en Cadena de la Polimerasa , Embarazo

RESUMEN

Evidence has shown that pre-eclampsia (PE) is associated with an increased level of catecholamines. Renalase is a catecholamine-metabolizing enzyme, which contributes to the occurrence of hypertension. In the current study, we aimed to assess the relation between two renalase gene ( RNLS) polymorphisms, including rs2576178 at the 5'-flanking region and rs10887800 at intron 6, near the exon/intron border and PE susceptibility. In this case-control study, 179 women with PE and 202 normotensive pregnant women were genotyped for RNLS rs2576178 and rs10887800 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. There was no association between RNLS rs10887800 and rs2576178 polymorphisms and PE, neither in the dominant nor in the recessive model. Although there was no association between RNLS rs10887800 polymorphism and mild PE, this polymorphism was associated with 2.2-fold higher risk of severe PE in the recessive model (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2-4.4; P = 0.01) but not in the dominant model. The RNLS rs2576178 and rs10887800 polymorphisms were not associated with PE severity. The RNLS rs10887800 and rs2576178 GG/GG combined genotypes were associated with 8.4- and 16.7-fold higher risk of PE and severe PE, respectively (OR, 8.4; 95% CI, 1-71.1; P = 0.048 and OR, 16.7; 95% CI, 1.6-167; P = 0.018). Also, the G-G haplotype was associated with 1.7-fold risk of PE and mild PE (OR, 1.7; 95% CI, 1.1-2.4; P = 0.009 and OR, 1.7; 95% CI, 1.1-2.5; P = 0.02). The RNLS rs10887800 polymorphism was associated with severe PE. The RNLS rs10887800 and rs2576178 GG/GG combined genotypes and G-G haplotype were associated with higher risk of PE.

Asunto(s)

Monoaminooxidasa/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Presión Sanguínea/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos/genética , Humanos , Hipertensión/genética , Irán , Preeclampsia/genética , Embarazo , Adulto Joven

RESUMEN

INTRODUCTION: Evidence has confirmed that placental/fetal hypoxia plays a key role in both endothelial cell dysfunction and PE pathogenesis. The aim of the present study was to investigate whether maternal/placental hypoxia-inducible factor1-α (HIF1-α) C1772T (rs11549465) and/or G1790A (rs11549467) polymorphisms and HIF1-α mRNA expression are associated with PE development. METHODS: The blood samples of 203 PE and 202 control women and the placenta of 86 PE and 84 control women were collected after delivery. The HIF1-α polymorphisms were genotyped using PCR- RFLP method. The mRNA expression levels were measured by Quantitative Real -Time PCR. RESULTS: The present study found no association between maternal HIF1-α rs11549465 and rs11549467 and placental rs11549467 polymorphisms and PE. However, the placental rs11549465 polymorphism was associated with PE in the dominant model. The CT/GG combined genotypes and TG haplotype of placental rs11549465 and rs11549467 polymorphisms were associated with higher risk of PE. The HIF1-α mRNA expression was 3-fold higher in the PE women. The rs11549465 TT genotype was associated with higher HIF1-α mRNA expression in PE women and in total population and rs11549467 GA genotype was associated with higher mRNA expression in total population. The relative mRNA expression of HIF1-α gene was higher in presence of CC/GA, TT/GG and TT/GA combined genotypes. CONCLUSION: This study found an association between placental but not maternal HIF1-α rs11549465 polymorphism and PE in the dominant model. The HIF1-α mRNA expression was higher in the placenta of PE women and was associated with rs11549465 and rs11549467 polymorphisms.

Asunto(s)

Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Placenta/metabolismo , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Adulto , Estudios de Casos y Controles , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Preeclampsia/epidemiología , Preeclampsia/metabolismo , Embarazo , ARN Mensajero/metabolismo , Factores de Riesgo , Adulto Joven

RESUMEN

Preeclampsia is a pathologic complication of pregnancy, associated with increased apoptosis in the cytotrophoblasts as the main cause of this disorder. Caspase-3 is a key apoptosis-related enzyme that both mitochondrial and death receptor apoptotic pathways can activate. In this study, we aimed to investigate the effect of placental CASP-3 rs4647602 and rs4647610 polymorphisms on PE susceptibility. The placentas of 106 PE women and 115 normotensive pregnant women were collected. Genomic DNA was extracted from the placenta. For genotyping of CASP-3 rs4647602 and rs4647610 polymorphisms, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used. The frequencies of placental CASP-3rs4647602CA and rs4647610GA genotypes were higher in PE women; however, the differences were not statistically different (P = 0.36 and P = 0.13, respectively). In addition, the frequencies of CA-GA combined genotypes and A-A haplotype were higher in PE women compared to the control women; however, the differences were marginally non-significant (P = 0.051 and P = 0.08, respectively). In-silico analysis revealed new enhancer and silencer motifs for mutant alleles of CASP-3rs4647602 and rs4647610 polymorphisms. In conclusion, placental CASP-3rs4647602 and rs4647610 polymorphisms were not associated with PE. Further studies with higher sample size are necessary to confirm or refute these findings.

Asunto(s)

Caspasa 3/genética , Simulación por Computador , Predisposición Genética a la Enfermedad , Placenta/enzimología , Polimorfismo Genético , Preeclampsia/genética , Proteínas Gestacionales/genética , Adulto , Caspasa 3/metabolismo , Femenino , Genotipo , Humanos , Preeclampsia/enzimología , Embarazo , Proteínas Gestacionales/metabolismo

RESUMEN

PURPOSE: PE is a pregnancy-specific complication, which genetic and epigenetic factors play key roles in its pathogenesis. DNA methylation is a main epigenetic alteration with important roles in gene regulation. Micro RNAs (miRNAs) as another member of epigenetic machinery regulate the gene expression and involve in different biological pathways including apoptosis and placental development. Therefore, the present study performed to assess the association between miRNA-34a promoter methylation and PE susceptibility. METHODS: The placenta of 104 PE pregnant women and 119 normotensive pregnant women were collected after delivery. The methylation status of the miRNA-34a promoter was assessed using Methylation Specific PCR (MSP). RESULTS: The frequency of the hemi-methylated (MU) miR-34a promoter was significantly lower in PE women compared to the controls (17.3 vs. 29.4%) (OR, 0.45 [95% CI, 0.2-0.9], P = 0.016). The overall methylation rate was 23.1% in PE women and 41.2% in the control group and was significantly lower in PE women (OR, 0.4 [95% CI, 0.2-0.8], P = 0.004). The frequency of hemi-methylated (MU) and overall methylated (MU+MM) promoter of miR-34a gene was significantly lower in severe PE but not in mild PE women compared to the controls [(OR, 0.3 [95% CI, 0.1-0.8], P = 0.02) and (OR, 0.3 [95% CI, 0.1-0.7], P = 0.009), respectively]. There was an association between hemi-methylated (MU) and overall methylated (MU+MM) promoter and late onset PE [(OR, 0.4 [95% CI, 0.2-0.9], P = 0.03) and (OR, 0.4 [95% CI, 0.2-0.8], P = 0.01), respectively]. CONCLUSIONS: An association was found between hypo-methylation of the miR-34a promoter and PE and PE severity.

RESUMEN

H19 is an imprinted gene transcribing a long noncoding RNA which was previously reported to be involved in some diseases. However, the association between the H19 polymorphisms and Pre-eclampsia (PE) susceptibility has remained elusive. This study aimed to evaluate the association between three H19 haplotype SNPs (rs3741219, rs217727, and rs2107425) and the risk of PE. The present case control study consisted of 193 PE women and 201 controls. The H19 rs3741219 and rs217727 polymorphisms were genotyped with PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) and the H19 rs2107425 polymorphism with ARMS-PCR (Amplification refractory mutation system) methods. The frequency of alleles and genotypes of H19 rs3741219 and rs2107425 polymorphisms did not differ between PE women and controls. The frequency of the H19 rs217727T allele was significantly higher in PE women (P < 0.0001). The H19 rs217727 polymorphism was associated with higher PE susceptibility in the Co-dominant (OR = 12.1, 95% CI = 5.7-24.5, P < 0.0001 for CT genotype and OR = 29.7, 95% CI = 12.9-68.1, P < 0.0001 for TT genotype), Dominant (OR = 15.1, 95% CI = 7.5-30.3, P = P < 0.0001), Recessive (OR = 4.5, 95% CI = 2.6-7.9, P = < 0.0001), and Over-dominant (OR = 2.1, 95% CI = 1.4-3.1, P = 0.0006) models. Furthermore, the CCC, TCT, TCC, and CCT haplotypes of H19 rs3741219, rs217727, rs2107425 were associated with lower risk of PE; however, the CTC, TTC, and TTT haplotypes were associated with higher risk of PE. In conclusion, the present study found the relationship between H19 rs217727 but not rs3741219 and rs2107425 polymorphisms and PE susceptibility. In addition, the CTC, TTC, and TTT haplotypes were associated with the higher risk of PE.

Asunto(s)

Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Preeclampsia/patología , ARN Largo no Codificante/genética , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Haplotipos , Humanos , Embarazo , Factores de Riesgo

RESUMEN

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.

Asunto(s)

ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Placenta/metabolismo , Polimorfismo de Nucleótido Simple , Preeclampsia/patología , ARN Mensajero/metabolismo , Ribonucleasa III/genética , Ribonucleasa III/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Preeclampsia/etiología , Preeclampsia/metabolismo , Embarazo , ARN Mensajero/genética