The association of ghrelin rs26311 and rs27647 polymorphisms and mRNA expression with preeclampsia susceptibility and severity-A case-control study.

OBJECTIVE: Ghrelin is an adipokine the placenta generates to control the maternal metabolic adaptation to pregnancy. It causes different pregnancy complications like preeclampsia (PE). Therefore, the aim of this study was to assess the association between ghrelin mRNA expression and rs26311 and rs27647 polymorphisms and PE development. METHODS: In total, 156 PE women (including 97 patients with mild PE and 59 patients with severe PE) and 152 healthy controls were recruited in this case-control study during 2019-2020. All participants with other diseases have been excluded from both groups. The ghrelin expression was analyzed with real-time PCR, and ghrelin variants were examined using the RFLP-PCR method. RESULTS: The maternal and placental ghrelin rs27647 and rs26311 variants were unrelated to PE susceptibility. Haplotype analyses showed no significant difference between the four haplotypes and PE. No relationship was revealed between rs27647 polymorphism and severe PE. However, the results indicated a relationship between rs27647 and severe PE compared to mild PE and controls. Therefore, the rs27647 variant was associated with severe PE compared to mild PE in codominant, recessive, and log-additive models and controls in codominant, dominant, recessive, and log-additive models. The placental ghrelin mRNA expression declined in PE women compared to controls (0.67-fold), but the difference was insignificant (p=0.263). No significant difference was found between various genotypes of rs27647 and rs26311 polymorphisms concerning ghrelin mRNA expression. CONCLUSION: The maternal and placental ghrelin polymorphisms, rs27647 and rs26311, showed no effect on PE. However, the rs27647 variant was associated with severe PE.

Positive correlation between Bax and Bcl-2 gene polymorphisms with the risk of endometriosis: A case-control study.

Background: Endometriosis is a chronic, gynecological disorder, and the disease's pathogenesis is still debatable. Genes related to apoptosis have been revealed to be deregulated in endometriosis. Objective: This study investigates the relationship between polymorphic variants of Bax -248G > A and Bcl-2 -938C > A promoter regions with endometriosis risk in an Iranian population. Materials and Methods: In this case-control study, the polymorphisms of Bax -248G > A and Bcl-2 -938C > A promoter regions were analyzed in 127 Iranian cases and 125 controls who were referred to Ali-ibn-Abi Taleb Educational hospital, Zahedan, Iran between May 2022 and February 2023. The genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequencies of mutant allele A carriers and the A allele of Bax -248G > A polymorphism showed about 2-fold significant increase of endometriosis risk (p = 0.04; p = 0.01, respectively). The frequencies of the mutant genotype AA and A allele carriers of Bcl-2 -938C > A polymorphism were approximately 4 and 2.5-fold higher in endometriosis compared to the control women, which were highly significant (p > 0.001). Moreover, the allele A frequency of Bcl-2 -938C > A was associated with a 2-fold higher risk of endometriosis (p > 0.001). Furthermore, the combination effects of these 2 single nucleotide polymorphisms showed that women with Bax -248G > A GGand Bcl-2 -938C > A AA variant alleles were associated with about 5 times higher risk of endometriosis (p > 0.001). Notably, a significant difference was observed in mutant allele distribution between minimal/mild (stage I and II) and moderate/severe (stage III and IV) women with endometriosis disease. Conclusion: The results of our study provide evidence that Bcl-2 -938C > A and Bax -248G > A single nucleotide polymorphisms might be associated with the risk of endometriosis.

The effects of NLRP3 rs10754558 and rs4612666 polymorphisms on preeclampsia susceptibility, onset, and severity: a case-control study and in silico analysis.

Preeclampsia (PE) is one of the serious complications of pregnancy and its exact etiology is unknown. Inflammasomes are multiportion complexes whose relation with PE has been described. Evidence showed the effect of NLRP3 inflammasome in PE pathogenesis. In the current study, we investigated the possible impacts of NLRP3 polymorphisms on PE. A total of 252 PE and 258 control pregnant women were selected for the study. The PCR-RFLP method was employed to genotype rs10754558 and rs4612666 polymorphisms. The RNAsnp and SpliceAid 2 software were used for in silico analysis. There was no relationship between NLRP3 polymorphisms and PE. In comparison to control women, the NLRP3 rs10754558 could increase the risk of severe PE in codominant and dominant models (OR=1.89, 95% CI=1.19-3.01, P=0.012, OR=1.95, 95% CI=1.24-3.06, P=0.0037, respectively). The findings of the in silico analysis revealed the effects of rs10754558 C to G and rs4612666 C to T substitutions on protein binding sites and rs10754558 C to G substitution on secondary RNA structure. These findings could confirm the finding those studies reported the impacts of these variants on various diseases. In conclusion, the NLRP3 rs10754558 variant was associated with an increased risk of EOPE and severe PE.

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.

Association between miR-202, miR-211, and miR-1238 gene polymorphisms and risk of vitiligo.

Vitiligo, as a common pigment defect in the skin, hair, and mucous membranes, results from the destruction of melanocytes. Recent investigations have shown that miRNA dysregulation contributes in the pathogenesis of vitiligo. Therefore, in this research, our aim is to explore the relationship between miR-202 rs12355840, miR-211 rs8039189, and miR-1238 rs12973308 polymorphisms and susceptibility to vitiligo. A total number of 136 vitiligo patients and 129 healthy individuals as a control group were included in this research. The salting out approach was implemented to extraction genomic DNA. The genetic polymorphisms of miR-202 rs12355840, miR-211 rs8039189, and miR-1238 rs12973308 were determined using PCR-RFLP approach. The findings revealed that miR-202 rs12355840 polymorphism under codominant (CT and TT genotypes), dominant, recessive, overdominant, and also allelic models is correlated with increased risk of vitiligo. In addition, codominant, dominant, overdominant, as well as allelic models of miR-211 rs8039189 polymorphism decrease risk of vitiligo. No significant relationship was observed between the miR-1238 rs12973308 polymorphism and susceptibility to vitiligo. The miR-211 rs8039189 polymorphism may serve a protective effect on vitiligo development and miR-202 rs12355840 polymorphism may act as a risk factor for vitiligo susceptibility.

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.

TIM-3/Gal-9 interaction affects glucose and lipid metabolism in acute myeloid leukemia cell lines.

Introduction: T-cell immunoglobulin and mucin domain-3 (TIM-3) is a transmembrane molecule first identified as an immunoregulator. This molecule is also expressed on leukemic cells in acute myeloid leukemia and master cell survival and proliferation. In this study, we aimed to explore the effect of TIM-3 interaction with its ligand galectin-9 (Gal-9) on glucose and lipid metabolism in AML cell lines. Methods: HL-60 and THP-1 cell lines, representing M3 and M5 AML subtypes, respectively, were cultured under appropriate conditions. The expression of TIM-3 on the cell surface was ascertained by flow cytometric assay. We used real-time PCR to examine the mRNA expression of GLUT-1, HK-2, PFKFB-3, G6PD, ACC-1, ATGL, and CPT-1A; colorimetric assays to measure the concentration of glucose, lactate, GSH, and the enzymatic activity of G6PD; MTT assay to determine cellular proliferation; and gas chromatography-mass spectrometry (GC-MS) to designate FFAs. Results: We observed the significant upregulated expression of GLUT-1, HK-2, PFKFB-3, ACC-1, CPT-1A, and G6PD and the enzymatic activity of G6PD in a time-dependent manner in the presence of Gal-9 compared to the PMA and control groups in both HL-60 and THP-1 cell lines (p > 0.05). Moreover, the elevation of extracellular free fatty acids, glucose consumption, lactate release, the concentration of cellular glutathione (GSH) and cell proliferation were significantly higher in the presence of Gal-9 compared to the PMA and control groups in both cell lines (p < 0.05). Conclusion: TIM-3/Gal-9 ligation on AML cell lines results in aerobic glycolysis and altered lipid metabolism and also protects cells from oxidative stress, all in favor of leukemic cell survival and proliferation.

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.

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.

Cancer Vaccine in Cold Tumors: Clinical Landscape, Challenges, and Opportunities.

The idea of cancer immunotherapy is to stimulate the immune system to fight tumors without destroying normal cells. One of the anticancer therapy methods, among many, is based on the use of cancer vaccines that contain tumor antigens in order to induce immune responses against tumors. However, clinical trials have shown that the use of such vaccines as monotherapy is ineffective in many cases since they do not cause a strong immune response. Particular tumors are resistant to immunotherapy due to the absence or insufficient infiltration of tumors with CD8+ T cells, and hence, they are called cold or non-inflamed tumors. Cold tumors are characterized by a lack of CD8+ T cell infiltration, the presence of anti-inflammatory myeloid cells, tumor-associated M2 macrophages, and regulatory T cells. It is very important to determine the stage of the antitumor response that does not work properly in order to use the right strategy. Applying other therapeutic methods alongside cancer vaccines can be more rational for cold tumors, which do not provoke the immune system strongly. Herein, we indicate some combinational therapies that have been used or are in progress for cold tumor treatment alongside vaccines.

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.

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.

TIM-3 in Leukemia; Immune Response and Beyond.

T cell immunoglobulin and mucin domain 3 (TIM-3) expression on malignant cells has been reported in some leukemias. In myelodysplastic syndrome (MDS), increased TIM-3 expression on TH1 cells, regulatory T cells, CD8+ T cells, and hematopoietic stem cells (HSCs), which play a role in the proliferation of blasts and induction of immune escape, has been reported. In AML, several studies have reported overexpression of TIM-3 on leukemia stem cells (LSCs) but not on healthy HSCs. Overexpression of TIM-3 on exhausted CD4+ and CD8+ T cells and leukemic cells in CML, ALL, and CLL patients could be a prognostic risk factor for poor therapeutic response and relapse in patients. Currently, several TIM-3 inhibitors are used in clinical trials for leukemias, and some have shown encouraging response rates for MDS and AML treatment. For AML immunotherapy, blockade TIM-3 may have dual effects: directly inhibiting AML cell proliferation and restoring T cell function. However, blockade of PD-1 and TIM-3 fails to restore the function of exhausted CD8+ T cells in the early clinical stages of CLL, indicating that the effects of TIM-3 blockade may be different in AML and other leukemias. Thus, further studies are required to evaluate the efficacy of TIM-3 inhibitors in different types and stages of leukemia. In this review, we summarize the biological functions of TIM-3 and its contribution as it relates to leukemias. We also discuss the effects of TIM-3 blockade in hematological malignancies and clinical trials of TIM-3 for leukemia therapy.

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).

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.

Vitamin D Receptor rs2228570 and rs731236 Polymorphisms are Susceptible Factors for Systemic Lupus Erythematosus.

BACKGROUND: The Vitamin D receptor (VDR) polymorphisms are the candidate genetic variants for susceptibility to different disease including autoimmune disorders. In the present study, we aimed to assess the association between VDR polymorphisms and systemic lupus erythematosus (SLE) susceptibility in Southeast Iranian population. MATERIALS AND METHODS: One hundred and twenty-seven patients with SLE and 139 controls were genotyped for VDR rs2228570, rs731236, and rs7975232 polymorphisms using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The VDR rs2228570 polymorphism was associated with higher risk of SLE in codominant, dominant, and overdominant models. Moreover, higher risk of SLE was observed in individuals with VDR rs731236 polymorphism in codominant, dominant, overdominant, and allelic models. The tAf haplotype of rs731236/rs7975232/rs2228570 polymorphisms was associated with higher risk of SLE. CONCLUSION: In conclusion, VDR rs2228570 and rs731236 polymorphisms and tAf haplotype were associated with SLE 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.