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 Genetic Polymorphisms in Long Noncoding RNA HOTTIP with Risk of Idiopathic Recurrent Spontaneous Abortion.

The clustered homeobox gene family known as the Hox family plays a fundamental role in the morphogenesis of the vertebrate's embryo. A long noncoding RNA (lncRNA), known as HOTTIP (HOXA transcript at the distal tip), has been functionally characterized and contributed to the pathogenesis of various conditions. The current case-control study was undertaken to examine the gene frequencies and shared alleles of the HOTTIP  gene in Iranian participants with or without idiopathic recurrent spontaneous abortion (RSA). Both ARMS-PCR reaction and RFLP-PCR techniques were employed to detect three HOTTIP polymorphisms (rs2023843C/T, rs78248039A/T, and rs1859168C/A) in a DNA sample of 161 women with RSA and 177 healthy women. We found that the TT genotype of the HOTTIP rs2023843 C/T polymorphism was associated with a lower risk for idiopathic RSA. In contrast, the TT genotype of the HOTTIP rs78248039 A/T polymorphism was correlated with an enhanced risk of RSA. The presence of the A-allele for HOTTIP rs1859168 C/A polymorphism was associated with an increased risk for idiopathic RSA. Haplotype analysis showed that the T/T/A, C/T/A, T/T/C, and T/A/A haplotypes of rs2023843/rs78248039/rs1859168 enhanced RSA susceptibility. Computational analysis predicted that this lncRNA might act as a potential sponge for some microRNAs; therefore, affecting the expression of genes being targeted by them. In addition, both rs2023843 and rs1859168 variants could alter the local secondary structure of HOTTIP. Our results showed that HOTTIP rs2023843C/T, rs78248039A/T, and rs1859168C/A polymorphisms may confer genetic susceptibility to idiopathic RSA in an Iranian population.

Impact of Survivin rs9904341 and rs17878467 Polymorphisms On Risk of Preeclampsia in Iran.

Preeclampsia (PE) is a hypertensive disorder that affects pregnancy, mother, and fetus. Early diagnosis of PE remains a challenge. This study aimed to investigate the association between survivin two (rs9904341 and rs17878467) SNPs and PE risk in healthy pregnant women compared to women with preeclampsia. A sample of 166 healthy pregnant women and 160 cases with preeclampsia was included and genotyped for rs9904341 with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and rs17878467 with amplification-refractory mutation system (ARMS) PCR. The genotypic and allelic assessments were performed using various statistical approaches. The frequency of rs9904341 and rs17878467 polymorphisms was not significantly different between PE and healthy pregnant women. rs9904341: codominant (p = 0.5), dominant (p = 0.24), recessive (p = 0.61), over-dominant model (p = 0.38), and log additive (p = 0.25). rs17878467: codominant (p = 0.41), dominant (p = 0.23), recessive (p = 0.4), over-dominant model (p = 0.42), and log additive (p = 0.24). The frequency of survivin rs9904341 CG and CC genotypes was higher in severe PE women compared to controls and this polymorphism was associated with PE severity only in the dominant model (OR = 1.84, CI 1.04-3.26, P = 0.034). There was a significant association between survivin rs9904341 polymorphism and PE severity. No relationship was found between survivin rs9904341 and rs17878467 polymorphisms and PE onset. The allelic and genotypic frequencies of survivin rs9904341 and rs17878467 polymorphisms are not significantly different between the preeclampsia and control groups in all genetic models. Haplotype analysis showed lower frequency G rs9904341 T rs17878467 haplotype in PE woman and this haplotype was associated with lower risk of PE (OR = 0.54, CI 0.33-0.91, P = 0.02).

Maternal and placental ANRIL polymorphisms and preeclampsia susceptibility.

Aim: The possible effects of maternal and placental ANRIL polymorphisms on preeclampsia were examined. Methods: The maternal blood of 315 preeclamptic and 317 control women and the placentas of 103 preeclamptic and 133 control women were enrolled in the study. ANRIL polymorphisms were genotyped using a PCR-RFLP method. Results: The maternal ANRIL rs1333048C variant showed a relationship with a lower risk of preeclampsia in codominant and dominant models. The maternal ANRIL rs4977574G variant had a relationship with a lower risk of preeclampsia in codominant and recessive models. There was an association between the placental rs1333048C variant and a lower risk of preeclampsia in codominant and dominant models. Conclusion: Maternal ANRIL rs1333048C and rs4977574G variants and placental rs1333048 variant showed a relationship with a lower risk of preeclampsia.

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.

An Association Between GAS5 rs145204276, NEAT1 rs512715, and MEG3 rs4081134 Gene Polymorphisms and Papillary Thyroid Carcinoma.

Background: This study explores the association between growth arrest-specific 5 (GAS5) rs145204276, nuclear paraspeckle assembly transcript 1 (NEAT1) rs512715, and Maternally Expressed 3 (MEG3) rs4081134 polymorphisms and their impact on susceptibility to papillary thyroid carcinoma (PTC), considering differential expression of long noncoding RNAs (lncRNAs) in PTC. Methods: A case-control study involving 125 papillary thyroid carcinoma (PTC) patients and 125 controls was conducted. Genotyping of polymorphisms was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. Results: No significant association was found between the two groups regarding genotypes and allelic frequencies of GAS-5 145204276 and MEG3 rs4081134 polymorphisms. Genetic models also showed the same results. Regarding NEAT1 rs512715, The PTC group had more GC genotypes and over-dominant models of NEAT1 rs512715 than controls, while controls showed a higher frequency of recessive models. Conclusion: GAS5 rs145204276 and MEG3 rs4081134 polymorphisms showed no significant association with papillary thyroid carcinoma (PTC) risk. In contrast, NEAT1 rs512715 exhibited a significant impact on PTC development.

Association of FOXO1 Rs17592236 Polymorphism and Tumor Size in Papillary Thyroid Carcinoma.

Background: A group of transcription factors involved in several cellular processes like cell growth, proliferation, cell cycle, differentiation and apoptosis which are critical to the cell biology of cancer is Forkhead Box O (FOXO) family. FOXOs are known as putative tumor suppressors. FOXO1 is a member of FOXO family which its abnormal expression or function has been indicated to promote cell proliferation and tumorigenesis. The probable effects of FOXO1 rs17592236 polymorphism on Papillary thyroid carcinoma (PTC) and its clinical findings were evaluated. Methods: In total, 156 PTC patients and 158 healthy subjects were participated in the study. Genotyping of FOXO1 rs17592236 polymorphism was carried out using RFLP-PCR method. Results: There was no association between the FOXO1 rs17592236 polymorphism and PTC in codominant, recessive, dominant, overdominant, and log-additive models. The frequency of rs17592236A allele was 13% in PTC and 17% in control group and were not statistically significant (p= 0.15). The analysis of the relationship between FOXO1 rs17592236 polymorphism and clinical specifications of papillary thyroid carcinoma demonstrated no significant relationship between rs17592236 polymorphism and PTC in different ages (< 40 and≥ 40), gender (male/female), extrathyroidal expansion, N stage, vascular invasion and capsular invasion in PTC patients. There was a relationship between FOX1 rs17592236 polymorphism and a larger tumor size (≥ 1 cm) only in log-additive model (OR= 2.96, 95% CI= 0.88-9.98; p= 0.04). Discussion: FOXO1 rs17592236 polymorphism was not associated with PTC; however, this variant was associated with a larger tumor size (≥ 1 cm) only in log-additive model.

Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study.

It has been established that microRNAs (miRNAs) are involved in the regulation of immune responses and serve as biomarkers of inflammatory diseases as well as recurrent spontaneous miscarriage (RSM). Herein, we aimed to study the relationship between three functional miR146a gene polymorphisms with idiopathic RSM (IRSM) susceptibility. We recruited 161 patients with IRSM and 177 healthy women with at least one live birth and without a history of abortion. Genotyping was performed using RFLP-PCR and ARMS-PCR methods. We found that the rs6864584 T/C decreased the risk of IRSM under dominant TT+TC vs. CC (OR = 0.029) and allelic C vs. T (OR = 0.028) contrast models. Regarding rs2961920 A/C and rs57095329 A/G polymorphisms, the enhanced risk of IRSM was observed under different genetic contrasted models, including the codominant CC vs. AA (OR = 2.81 for rs2961920) and codominant GG vs. AA (OR = 2.36 for rs57095329). After applying a Bonferroni correction, haplotype analysis revealed a 51% decreased risk of IRSM regarding the ACA genotype combination. This is the first study reporting that miR146a rs57095329 A/G, rs2961920A/C, and rs6864584 T/C polymorphisms are associated with the risk of IRSM in a southern Iranian population. Performing replicated case-control studies on other ethnicities is warranted to outline the precise effects of the studied variants on the risk of gestational trophoblastic disorders.

Correlation between adiponectin rs2241766 and rs266729 polymorphisms and risk of papillary thyroid cancer.

About 60-80% of thyroid cancer (TC) cases are papillary thyroid cancer (PTC). Studies have shown that serum adiponectin levels are inversely related to the risk of TC and PTC. Aim of the present study was to evaluate the association between adiponectin rs2241766 and rs266729 polymorphisms and risk of PTC. 122 PTC patients and 128 healthy subjects were enrolled in the study. PCR-RFLP and ARMS-PCR methods were used for genotype analysis. The rs266729 polymorphism did not correlate with risk of PTC. As regard rs2241766 polymorphism, the frequency of the GG genotype did not have a significant difference between the two groups, although, PTC cases showed higher frequency of GT genotype compared to controls (OR=2.87, 95% CI=1.56-5.28, P=0.001). We observed a significant association between adiponectin rs2241766 polymorphism and PTC, however, our result showed no significant relationship between adiponectin rs266729 polymorphism and risk of PTC.

Association of IL-1ß, NLRP3, and COX-2 Gene Polymorphisms with Autoimmune Thyroid Disease Risk and Clinical Features in the Iranian Population.

BACKGROUND: Grave's disease (GD) and Hashimoto's thyroiditis (HT) are autoimmune diseases of the thyroid gland in which genetic predisposition plays a major role in their development. Currently, the role of NLRP3 inflammasome and COX-2 has been documented in many autoimmune diseases. The purpose of the study is to delineate the impact of IL-1ß (rs1143634), NLRP3 (rs3806265), and COX-2 (rs2745557) gene polymorphisms in the development of GD and HT. METHODS: A total of 256 newly diagnosed patients with autoimmune thyroid disease (135 patients with HT and 121 GD patients) as case groups and 145 controls were included in the study. RESULTS: Recessive and overdominant models showed a significant association between IL-1ß rs1143634 SNP and HT development risk. The frequency of TT genotype and T allele of IL-1ß rs1143634 SNP in the control group was significantly higher than the GD group. There was no significant association between NLRP3 rs3806265 polymorphism and HT and GD development. The frequency of GA genotype of COX-2 (rs2745557) in the control group was significantly higher than that in the HT group. There was no significant association between COX-2 rs2745557 genotypic and allelic distribution and GD development risk. The results revealed a significant relationship between some clinical features of HT and GD groups and SNPs studied. CONCLUSION: The results manifest the significant impact of IL-1ß rs1143634 and COX-2 (rs2745557) SNPs and HT development and IL-1ß rs1143634 SNP on GD occurrence risk. Furthermore, a significant relationship was observed between some clinical features of HT and GD groups and studied SNPs.

The Effect of Renalase rs2576178 and rs10887800 Polymorphisms on Ischemic Stroke Susceptibility in Young Patients (<50 Years): A Case-Control Study and In Silico Analysis.

BACKGROUND: Ischemic stroke (IS) is the most common form of cerebrovascular accident which its precise etiology remains mysterious. Renalase is a catecholamine-degrading enzyme playing a major role in blood pressure control. Recent studies show the effect of renalase activity on various diseases like IS. In the current study, we examined the possible effects of renalase gene (RNLS) rs2576178 and rs10887800 variants at the 5'-flanking and intron 6 regions on IS, respectively. METHODS: One hundred and fifty-four IS patients younger than 50 years and 165 age- and sex-matched controls were recruited in the study. For genotyping of rs2576178 and rs10887800 variants, the PCR-RFLP method was used. RESULTS: The RNLS rs10887800 AG genotype was more repeated in IS patients, but the difference was marginally nonsignificant (P = 0.054). This variant was associated with IS in the overdominant model, and the AG genotype is associated with a1.6-fold increased risk of IS compared to AA+ GG genotypes (OR = 1.6, 95% CI: 1-2.5, P = 0.033). No relationship was observed between RNLS rs2576178 polymorphism and IS in all genetic models. The findings of the haplotype and combination effects of rs10887800 and rs2576178 variants on IS showed no significant association. The in silico analysis showed no effect of rs2576178 and rs10887800 polymorphisms in the RNA structure, but the alteration of RNA sequence in rs2576178 results in the lack of a MBNL1 protein binding site. CONCLUSIONS: RNLS rs10887800 but not rs2576178 polymorphism was associated with IS susceptibility in the overdominant model (AG vs AA+ GG genotypes).

Genetic variants of HOTAIR are associated with susceptibility to recurrent spontaneous abortion: A preliminary case-control study.

AIM: To investigate the association between Hox transcript antisenses RNA (HOTAIR) polymorphisms, rs12826786 C/T, rs920778 T/C, rs4759314 A/G, and rs1899663 G/T, with recurrent spontaneous abortion (RSA) susceptibility in the Iranian women. METHODS: We enrolled 161 patients diagnosed with RSA and 177 healthy women with at least one live birth without a history of abortion. Genotyping of HOTAIR polymorphisms was carried out using both restriction fragment length polymorphism-polymerase chain reaction and amplification refractory mutation system-polymerase chain reaction methods. Odds ratios (ORs) with 95% confidence intervals (CIs) were assessed to estimate the strength of association. RESULTS: Different inheritance models of rs12826786 C/T, rs920778 T/C, and rs1899663 G/T polymorphisms significantly enhanced the risk of RSA (p < 0.05), whereas the rs4759314 A/G polymorphism was correlated with diminished risk of developing RSA under recessive AA versus GA + GG (OR 0.42 [95% CI = 0.19-0.91]), log-additive GG versus GA vs. GG (OR 0.67 [95% CI = 0.48-0.93]), and allelic A versus G (OR 0.65 [95% CI = 0.47-0.92]) models. Moreover, the TGTC, TTCT, TTTC, CGTC, CGTT, CTCC, CTCT, CTTC, and CTTT haplotypes of rs920778/rs1899663/rs12826786/ significantly increased the risk of RSA. The studied variants were not in strong linkage disequilibrium. CONCLUSIONS: Our results indicated that variations in the HOTAIR gene might serve as beneficial biomarkers for determining susceptibility to RSA. To confirm these findings, replication studies with a larger population and different races are needed.

Effects of the MTOR and AKT1 genes polymorphisms on papillary thyroid cancer development.

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer, comprising 80% of all thyroid malignancies. The phosphoinositide-3-kinase-protein kinase B/Akt (PI3K-PKB/Akt) pathway is a main pathway in control of cell growth. Activated mTOR and Akt are involved in the development and progression of the PTC. This study aimed to evaluate the effects of MTOR (rs2536 and rs2295080) and AKT1 (rs2494732, rs1130214, and rs1130233) polymorphisms on PTC susceptibility. This study was conducted on 131 PTC patients and 144 healthy subjects. Genotype analysis was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Our results showed no statistically significant association between MTOR rs2536, AKT1 rs2494732, and rs1130214 polymorphisms and PTC development. However, MTOR rs2295080 polymorphism was found to be associated with a decreased risk of PTC in dominant and allelic models. The TT genotype of AKT1 rs1130233 was significantly higher in the PTC group in comparison to the controls, with a 3.5-fold increased risk for developing PTC. Furthermore, the allelic distribution also showed the T allele of rs1130233 as a risk factor for PTC occurrence. In conclusion, our results suggest the MTOR rs2295080 and AkT1 rs1130233 as the protective and risk factors for PTC development, respectively.

The Impact of TRAIL (C1595T and G1525A) and DR4 (rs20576) Gene Polymorphisms on Systemic Lupus Erythematosus.

Apoptosis dysregulation is a distinct hallmark of several disorders like systemic lupus erythematosus (SLE). In fact, SLE has two special features for apoptosis: irregular apoptosis and decline in clearing of apoptotic bodies. Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) is a death ligand that causes to apoptosis via attaching to its receptors such as death receptor-4 (DR4). The present study aimed to evaluate the effects of TRAIL G1525A and C1595T and DR4 A683C (rs20576) gene polymorphisms on SLE development. 160 SLE patients and 160 healthy individuals as the control group participated in the study. Genotype analysis was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). With regard to TRAIL (C1595T) polymorphism, the frequency of CT genotype was significantly higher in the case group than the control with 3-fold increase in SLE development risk (P = 0.0001). Furthermore, the frequency of the TT genotype also was higher in the case group than the control group with 3.2-fold increase in SLE development risk. The allelic distribution analysis defined the T allele as a risk factor for SLE development (P = 0.0001). The frequency of AA genotype and allele A of TRAIL (G1525A) polymorphism also was statistically higher in the case group than the control group (P = 0.0001). There was no significant association between DR4 rs20576 polymorphism and SLE development. TRAIL C1595T and G1525A gene polymorphisms are suggested as the risk factors for SLE development, although the results showed no association between DR4 rs20576 polymorphism and SLE.

The effects of the genetic polymorphisms of antioxidant enzymes on susceptibility to papillary thyroid carcinoma.

Several lines of evidences have indicated that inflammation play an important role in the carcinogenesis. During the inflammatory processes, free radical species are produced from oxidative stress. In normal conditions, enzymatic and nonenzymatic antioxidants remove these products. Manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPx-1), and catalase (CAT) are three important enzymes. Therefore, this study aimed to evaluate the effects of MnSOD (SOD2), GPX-1, and CAT genetic polymorphisms on papillary thyroid carcinoma (PTC) susceptibility. A total of 134 patients with PTC and 151 healthy controls were recruited to participate in this study. All samples were genotyped for SOD2 rs4880, GPX1 1050450, and CAT rs7943316 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism method. The frequencies of the rs1050450, rs4880, and rs7943316 alleles and genotypes were not different between PTC patients and controls. However, the TC genotype of SOD2 rs4880 polymorphism was significantly higher in males compared to that in females in PTC patients (odds ratio [OR], 3.9 [95% CI, 1.5-11], p = .007). The rs4880 polymorphism was also associated with higher stages (III-IV) of PTC in dominant model. No significant correlation was found between GPX1-rs1050450 and CAT-rs7943316 polymorphisms and demographic, clinical, and pathological features of the disease. The SOD2 rs4880CT genotype was more frequent in males with PTC and patients with higher stages (III-IV) of disease (OR, 2.9 [95% CI, 1.1-7.7], p = .04). However, no significant association was found between GPX1-rs1050450 and CAT-rs7943316 variants and PTC or its demographic, clinical, and pathological features.

The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features.

Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Genetic polymorphisms of the TP53 and P21 genes are the candidate variants in various cancers development. This study investigated whether the polymorphisms in TP53 (rs1042522) and P21 (rs1059234 and rs1801270) affect the risk of PTC and whether such the genotype of these polymorphisms is associated with pathological and clinical characteristics of PTC. A case-control study was conducted with 286 Iranian people, including 131 PTC cases and 155 healthy controls. The genetic polymorphisms were investigated by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results suggested that TP53-rs1042522 CC genotype was significantly associated with protection against PTC, in the dominant, recessive and allelic models (OR = 0.4, 95%CI: 0.2-0.8, P = .008; OR = 0.5, 95%CI: 0.3-0.9, P = .01; OR = 0.6, 95%CI: 0.4-0.8, P = .002, respectively). The rs1042522 was associated with PTC patients with tumor size greater than 1 cm in dominant and recessive models (OR = 0.2, 95%CI = 0.04-0.9, P = .04 and OR = 0.3, 95%CI = 0.1-0.7, P = .009, respectively) and was associated with vascular invasion in dominant model (OR = 0.3, 95%CI = 0.1-0.7, P = .01). No correlation was identified between P21 rs1059234 and rs1801270 polymorphisms and risk of PTC and pathological and clinical characteristics of PTC. Genetic variations in rs1042522 might alter the PTC risk, which could affect tumor size and cause lower incidence of vascular invasion in PTC cases. This was the first report suggesting that no correlation was found between P21 rs1059234 and rs1801270 polymorphisms and PTC risk. Thus, more studies with a larger population size and different ethnic groups and functional assays are needed to confirm our results.

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.

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.