The effects of ANRIL polymorphisms on colorectal cancer, tumor stage, and tumor grade among Iranian population.

BACKGROUND: Colorectal cancer (CRC) is a type of neoplasm, developing in the colon or rectum. The exact etiology of CRC is not well known, but the role of genetic, epigenetic, and environmental factors are established in its pathogenesis. Therefore, the aim of this research was to explore the effects of ANRIL polymorphisms on the CRC and its clinical findings. METHODS AND RESULTS: The peripheral blood specimens were collected from 142 CRC patients and 225 controls referred to Milad Hospital, Tehran, Iran. PCR- RFLP method was used to analyze ANRIL rs1333040, rs10757274 rs4977574, and rs1333048 polymorphisms. The ANRIL rs1333040 polymorphism was related to a higher risk of CRC in the co-dominant, dominant, and log-additive models. ANRIL rs10757274, rs4977574, and rs1333048 polymorphisms showed no effect on CRC susceptibility. The CGAA and TGGA haplotypes of ANRIL rs1333040/ rs10757274/ rs4977574/rs1333048 polymorphisms were associated with the higher and the lower risk of CRC respectively. The rs1333040 polymorphism was associated with higher TNM stages (III and IV). The frequency of ANRIL rs10757274 polymorphism was lower in CRC patients over 50 years of age only in the dominant model. In addition, the rs10757274 was associated with well differentiation in CRC patients. CONCLUSION: The ANRIL rs1333040 polymorphism was associated with a higher risk of CRC and higher TNM stages. ANRIL rs10757274 polymorphism was associated with the well-differentiated tumor in CRC.

The possible effects of the MTOR polymorphisms on preeclampsia susceptibility, severity, and onset: a case-control study and in silico analysis.

BACKGROUND: Preeclampsia (PE) is a gestational complication with developed hypertension and proteinuria. Evidence showed the role of mTOR in various cellular processes. Therefore, this study aimed to evaluate the effects of MTOR polymorphisms on susceptibility, severity, and onset of Preeclampsia (PE). METHODS AND RESULTS: A total of 250 PE pregnant women and 258 age-matched control subjects were recruited in this study. To genotype MTOR polymorphisms, the PCR-RFLP method was used. The SpliceAid 2 and PROMO tools were used for in silico analysis. The maternal MTOR rs17036508T/C polymorphism was associated with PE risk in various genetic models. There was no relationship between rs2536T/C and rs2295080T/G polymorphisms and PE. The TTC and TGC haplotypes of rs2536/ rs2295080/ rs17036508 polymorphisms were significantly higher in PE women. Subgroup analysis revealed the association between the MTOR rs2295080 variant and an increased risk of Early-onset PE (EOPE). However, the MTOR rs17036508 was associated with a higher risk of EOPE and Late- Onset PE. In addition, the MTOR rs2295080 could increase the risk of severe PE. The results of the in silico analysis showed that rs17036508 disrupted several binding motifs in the mutant sequence. The PROMO database revealed that the T to C substitution leads to the loss of the TFII-I binding site in the mutant allele. CONCLUSION: The MTOR rs17036508T/C polymorphism was associated with PE risk. There was an association between the MTOR rs2295080 variant and an increased risk of EOPE. The MTOR rs17036508T/C and rs2295080T/C variants could disrupt several binding motifs and TFII-I binding respectively.

Association of AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms with papillary thyroid carcinoma: A case-control study.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer which its precise etiology remains unknown. However, environmental and genetic factors contribute to the etiology of PTC. Axis inhibition protein 1 (Axin1) is a scaffold protein that exerts its role as a tumor suppressor. In addition, Cathepsin B (Ctsb) is a cysteine protease with higher expression in several types of tumors. Therefore, the aim of this study was to investigate the possible association of AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms with PTC susceptibility. MATERIALS & METHODS: In total, 156 PTC patients and 158 sex-, age-, and BMI-matched control subjects were enrolled in the study. AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms were genotyped using the PCR-RFLP method. RESULTS: There was a relationship between AXIN1 rs12921862 C/A polymorphism and an increased risk of PTC in all genetic models except the overdominant model. The AXIN1 rs1805105 G/A polymorphism was associated with an increased PTC risk only in codominant and overdominant models. The frequency of AXIN1 Ars12921862 Ars1805105 haplotype was higher in the PTC group and also this haplotype was associated with an increased risk of PTC. Moreover, the AXIN1 rs12921862 C/A polymorphism was not associated with PTC clinical and pathological findings, but AXIN1 rs1805105 G/A polymorphism was associated with almost three folds of larger tumor size (≥1 cm). There was no association between CTSB rs12898 G/A polymorphism and PTC and its findings. CONCLUSION: The AXIN1 rs12921862 C/A and rs1805105 G/A polymorphisms were associated with PTC. AXIN1 rs1805105 G/A polymorphism was associated with higher tumor size.

Role of rare immune cells in common variable immunodeficiency.

Common variable immunodeficiency disorder (CVID) is a heterogeneous disorder and the most common symptomatic antibody deficiency disease characterized with hypogammaglobulinemia and a broad range of clinical manifestations. Multiple genetic, epigenetic, and immunological defects are involved in the pathogenesis of CVID. These immunological defects include abnormalities in the number and/or function of B lymphocytes, T lymphocytes, and other rare immune cells. Although some immune cells have a relatively lower proportion among total immune subsets in the human body, they could have important roles in the pathogenesis of immunological disorders like CVID. To the best of our knowledge, this is the first review that described the role of rare immune cells in the pathogenesis and clinical presentations of CVID.

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

BACKGROUND: Recurrent 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. METHODS: In this case-control study, 150 RSA patients and 195 age-matched healthy female controls were recruited. Both polymorphisms were genotyped using PCR-RFLP method. RESULTS: The 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. CONCLUSION: the 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.

The possible role of maternal and placental vitamin D receptor polymorphisms and haplotypes in pathogenesis of preeclampsia.

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.

Renalase rs10887800 polymorphism is associated with severe pre-eclampsia in southeast Iranian women.

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.

Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia.

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.

Association of HOTAIR gene polymorphisms and haplotypes with uterine leiomyoma susceptibility in southeast of Iran.

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.

The effect of miR-146a rs2910164 and miR-149 rs2292832 polymorphisms on preeclampsia susceptibility.

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.

The effect of GPx-1 rs1050450 and MnSOD rs4880 polymorphisms on PE susceptibility: a case- control study.

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.

The association of pri-miRNA- 26a1 rs7372209 polymorphism and Preeclampsia susceptibility.

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.

Common Variations in Prothrombotic Genes and Susceptibility to Ischemic Stroke in Young Patients: A Case-Control Study in Southeast Iran.

Background and Objective: Evidence indicates that genetic factors may be involved in the risk of ischemic stroke (IS). The aim of this study was to assess the effect of genetic polymorphisms located in exons or untranslated regions of MTHFR as well as FV genes on ischemic stroke. Materials and Methods: In this case-control study, 106 patients with IS and 157 healthy volunteers (age <50 years) were genotyped for MTHFR C677T, A1298C, C2572A and C4869G, FVL, and prothrombin G20210A polymorphisms. Results: The MTHFR 677CT genotype was more frequent in patients and increased risk of IS with Odds Ratio = 1.9. The MTHFR A1298C and C2572A polymorphisms were not associated with IS in dominant and recessive models. Our findings showed a significant decrease in the MTHFR 4869CG genotype in IS patients, and this variant was associated with a decreased risk of IS in the dominant model. The CAAT haplotype was associated with increased risk, and the GAAC haplotype was associated with decreased risk of IS compared to other haplotypes. There was no relation between FVL G1691A polymorphism and IS risk. Conclusions: The present study showed that the MTHFR 677CT genotype was more frequent and the MTHFR 4869CG genotype was less frequent in young IS patients.

The association of the placental CASPASE-3 gene polymorphisms and preeclampsia susceptibility and in-silico analysis.

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.

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.

Association between maternal circulating IL-27 levels and preeclampsia.

In this study, we investigated the relationship between serum level of IL-27 with preeclampsia and its severity. Fifty-six preeclamptic, 21 health pregnant and 20 health nonpregnant women formed the study group. The levels of IL-27 in maternal circulation were determined by ELISA. IL-27 serum levels were found to be elevated in healthy pregnant and preeclamptic groups as compared to non-pregnant women, this increase was significant in preeclamptic cases (p=0.0004). Moreover, a significant difference of IL-27 serum level was observed between groups and the healthy pregnant controls, (p=0.0095). Notably, the level of IL-27 was considerably elevated in women with severe preeclampsia, but not with mild preeclampsia as compared with healthy pregnant women (p=0.0056, p=0.0964, respectively). Furthermore, IL-27 serum levels were significantly differences in early onset and late onset sever preeclampsia than in gestation matched healthy pregnancies (p=0.0376, p=0.0085, respectively). In conclusion, our results suggest IL-27 might be a useful biomarker for disease severity in preeclampsia.

Hypomethylation of the miRNA-34a gene promoter is associated with Severe Preeclampsia.

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.

The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility.

PURPOSE: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. METHODS: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1-2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4-6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC-GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4-8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 - 2], P = 0.01). CONCLUSIONS: The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC-GG combined genotype and C-G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.

The ID genotype of MDM2 40 bp insertion/deletion polymorphism was associated with lower risk of SLE.

BACKGROUND: In patients with systemic lupus erythematosus (SLE), loss of immunological tolerance to self-nuclear antigens and abnormal activation of self-reactive T and B cells lead to self-antibodies and immune complex production. The autoreactive lymphocytes are removed by the apoptotic process in healthy individuals; however, apoptosis disruption could cause accumulation of apoptotic bodies and nuclear debris. Therefore, apoptosis plays a crucial role in the pathogenesis of autoimmune diseases. PURPOSE: To investigate the association between two polymorphisms in an apoptotic-related gene, MDM2, and SLE. STUDY DESIGN: A case-control study was conducted on 200 patients with SLE and 206 healthy volunteers matched for age, sex, and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR methods were used for genotyping. RESULTS: No association was found between the MDM2 T309G polymorphism (rs2279744) and SLE. The ID genotype of the insertion/deletion (I/D) polymorphism (rs3730485) was significantly lower in patients with SLE, and the ID genotype could be a protective factor for SLE. The DD genotype was not associated with SLE. The frequency of combined TT/ID and GG/ID genotypes of MDM2 T309G and I/D polymorphisms was lower in the patients with SLE and was associated with a lower risk of SLE. The frequency of the TD haplotype of MDM2 T309G and I/D polymorphisms was significantly lower in patients with SLE and could reduce the SLE risk. CONCLUSIONS: The ID genotype of the MDM2 I/D polymorphism was associated with a lower risk of SLE. There was no association between MDM2 T309G polymorphism and SLE.

The MDM2 promoter T309G polymorphism was associated with preeclampsia susceptibility.

PURPOSE: Preeclampsia (PE) is a hypertensive disorder of pregnancy in which abnormal proliferation and apoptosis of placenta trophoblast has a pivotal role in its pathophysiology. The aim of the current study was to examine the association between Mouse Double Minute 2 (MDM2) T309G and 40 bp insertion/deletion (I/D) polymorphisms and PE risk. METHODS: A case-control study was conducted on 208 PE women and 164 healthy pregnant women matching age, sex, and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR methods were used for genotyping. RESULTS: The MDM2 309GG genotype was associated with PE, and this genotype was found to be a risk factor for PE. There was no association between the MDM2 I/D polymorphism and PE. The haplotype-based association analysis revealed no association between MDM2 T309G and 40 bp I/D polymorphisms and PE. The frequency of TT-DD and GG-DD combined genotypes were significantly higher in PE women with marginal P values (P = 0.046). CONCLUSIONS: The MDM2 309GG genotype was associated with higher risk of PE. The TT-DD and GG-DD combined genotypes were higher in PE women.