Immune gene polymorphisms associated with poor response to platelet transfusion and recombinant factor VII administration in Glanzmann thrombasthenia.

INTRODUCTION: Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. AIMS: We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. METHODS: We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-α were analysed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. RESULTS: In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-α rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. CONCLUSIONS: These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1α, IL1-ß, IL-1R1 and IL-R antagonists might be involved in the GT progression.

Genetic Variations of Angiotensinogen, Angiotensin Converting Enzyme, and Angiotensin Type 1 Receptor with the Risk of Pulmonary Tuberculosis.

There is little data regarding the impact of renin-angiotensin system (RAS) gene polymorphisms on tuberculosis. The current study designed to survey the possible association between RAS polymorphisms and the risk of pulmonary tuberculosis (PTB) in a sample of the southeast Iranian population. This case-control study was done on 170 PTB patients and 170 healthy subjects. The AGT rs699 C>T, ACE rs4341 C>G and AT1R rs5186 C>A variants were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and ACE rs4646994 (287bp I/D) variant by PCR method. Regarding AT1R rs5186 A>C polymorphism, the findings revealed that AC genotype and C allele significantly decreased the risk of PTB (OR=0.39, 95% CI=0.22-0.67, p=0.001, and OR=0.53, 95% CI=0.25-0.72, p=0.002, C vs. A, respectively). The TC genotype and C allele of AGT rs699 T>C significantly associated with decreased the risk of PTB (OR=0.45, 95% CI=0.28-0.74, p=0.002, TC vs. TT and OR=0.51, 95% CI=0.32-0.80, p=0.005, C vs. T, respectively). The ID genotype of ACE 287bp I/D significantly increased the risk of PTB (OR=1.88, 95% CI=1.12-3.17, p=0.017). Our finding did not support an association between ACE rs4341 C>G variant and the risk of PTB. In summary, the findings revealed an association between AT1R rs5186 A>C, AGT rs699 T>C and ACE 287bp I/D polymorphisms and the risk of PTB in a sample of the southeast Iranian population. Further investigation with higher sample sizes and diverse ethnicities are required to confirm our findings.

Novel variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability in Iranian consanguineous families.

BACKGROUND: Intellectual disability (ID) is a heterogeneous group of neurodevelopmental disorders that is characterized by significant impairment in intellectual and adaptive functioning with onset during the developmental period. Whole-exome sequencing (WES)-based studies in the consanguineous families with individuals affected with ID have shown a high burden of relevant variants. So far, over 700 genes have been reported in syndromic and non-syndromic ID. However, genetic causes in more than 50% of ID patients still remain unclear. METHODS: Whole-exome sequencing was applied for investigation of various variants of ID, then Sanger sequencing and in silico analysis in ten patients from five Iranian consanguineous families diagnosed with autosomal recessive neurodevelopmental disorders, intellectual disability, performed for confirming the causative mutation within the probands. The most patients presented moderate-to-severe intellectual disability, developmental delay, seizure, speech problem, high level of lactate, and onset before 10 years. RESULTS: Filtering the data identified by WES, two novel homozygous missense variants in FBXO31 and TIMM50 genes and one previously reported mutation in the CEP290 gene in the probands were found. Sanger sequencing confirmed the homozygote variant's presence of TIMM50 and FBXO31 genes in six patients and two affected siblings in their respective families. Our computational results predicted that the variants are located in the conserved regions across different species and have the impacts on the protein stability. CONCLUSION: Hence, we provide evidence for the pathogenicity of two novel variants in the patients which will expand our knowledge about potential mutation involved in the heterogeneous disease.

Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study.

Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00-5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30-6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97-5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62-4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37-2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

Association Study of MBL2 Gene Polymorphisms and Risk of Tuberculosis in Southeast of Iran.

Mannose-binding lectin (MBL) is an acute phase protein which recognizes the pathogens through its carbohydrate recognition domain. It is an important part of human innate immunity. The aim of the current study was to evaluate the impact of MBL2 polymorphism on pulmonary tuberculosis in a number of patients from the southeast of Iran. In this case-control study, 2 MBL gene polymorphisms (rs1800450, rs7095891) were genotyped using PCR-RFLP method and polymerase chain reaction for detection of 34bp ins/del of MBL2 gene (rs777980157) polymorphism. The study included 170 patients with PTB (pulmonary tuberculosis) and 175 control subjects. The findings indicated that the GA (GA vs. GG: OR=0.172, 95% CI=0.107-0.275, P<0.001) (OR - odds ratio; CI - confidence interval) genotype as well as GA+AA (GA+AA vs. GG: OR=0.191, 95% CI=0.120-0.302, P<0.001) genotype of rs1800450 reduced the risk of PTB compared to GG genotype. The rs7095891 variant significantly decreased the risk of PTB in codominant (GA vs. GG: OR=0.118, 95% CI=0.054-0.258, P<0.001; and AA vs. GG: OR=0.029, 95% CI=0.01-0.082, P<0.001), dominant (GA+AA vs. GG: OR=0.095, 95% CI=0.044-0.207, P<0.001) and recessive (AA vs. GA+GG: OR=0.172, CI=0.081-0.365, P<0.001) inheritance models. No significant relationship was identified between the rs777980157 variant and PTB risk/protection. In conclusion, we found that the MBL2 rs1800450 and rs7095891 polymorphisms provide relative protection against PTB. Additional studies on larger populations with different ethnicities are required to verify our findings.

Association between P2X7 Polymorphisms and Susceptibility to Tuberculosis: An Updated Meta-Analysis of Case-Control Studies.

Background and Objectives: Several studies inspected the impact of P2X7 polymorphisms on individual susceptibility to tuberculosis (TB), but the findings are still controversial and inconclusive. To achieve a more precise estimation, we conducted a meta-analysis of all eligible studies on the association between P2X7 polymorphisms and TB risk. Materials and Methods: Relevant studies were identified by searching the PubMed, Web of Science, Scopus and Google scholar databases up to November 2018. Twenty-four full-text articles were included in our meta-analysis. The strength of association between P2X7 polymorphisms and TB risk was evaluated by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models. Results: The findings of this meta-analysis revealed that the rs3751143 variant significantly increased the risk of TB in heterozygous codominant (OR = 1.44, 95%CI = 1.17-1.78, p = 0.0006, AC vs. AA), homozygous codominant (OR = 1.87, 95% CI = 1.40-2.49, p = 0.0004, CC vs. AA), dominant (OR = 1.50, 95% CI = 1.22-1.85, p = 0.0002, AC + CC vs. AA), recessive (OR = 1.61, 95% CI = 1.25-2.07, p = 0.001, CC vs. AC + AA), and allele (OR = 1.41, 95% CI = 1.19-1.67, p < 0.0001, C vs. A) genetic models. Stratified analysis showed that rs3751143 increased the risk of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in all genetic models. Furthermore, the rs3751143 increased risk of TB in the Asian population. The findings did not support an association between the rs2393799, rs1718119, rs208294, rs7958311, and rs2230911 polymorphisms of P2X7 and TB risk. Conclusions: The findings of this meta-analysis suggest that P2X7 rs3751143 polymorphism may play a role in susceptibility to TB in the Asian population. More well-designed studies are required to elucidate the exact role of P2X7 polymorphisms on TB development.

4-bp insertion/deletion (rs3783553) polymorphism within the 3'UTR of IL1A contributes to the risk of prostate cancer in a sample of Iranian population.

Growing evidence demonstrated the presence of an association between IL1A rs3783553 polymorphism and the risk of various cancers. We aimed to evaluate whether the 4-bp insertion/deletion polymorphism (rs3783553) within the 3' untranslated region (3'UTRs) of IL1A was associated to the risk of prostate cancer (PCa) in a sample of Iranian population. A case-control study, including 150 prostate cancer patients and 155 healthy men, was done to examine the possible association between IL1A 4-bp ins/del polymorphism and PCa risk in a sample of southeast Iranian population. Mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was designed for genotyping the studied variant. Our findings showed that 4-bp ins/del polymorphism significantly increased the risk of PCa in codominant, recessive and allelic inheritance model. We also evaluated the association between the IL1A 4-bp ins/del polymorphism and clinicopathological characteristics of the patients, and found a significant association between 4-bp ins/del variant and stage, perineural invasion and surgical margin of tumor samples. Bioinformatics analysis revealed that the ins/del variant affected the IL1A mRNA stability leading to a structural shift in IL1A mRNA and has-miR-125a-3p hybrid. In conclusion, our findings proposed an association between IL1A 4-bp ins/del polymorphism and PCa risk. Additional studies with enlarged sample size and diverse ethnicities are required to validate our finding.

Evaluation of 4-bp insertion/deletion polymorphism within the 3'UTR of SGSM3 in bladder cancer using mismatch PCR-RFLP method: A preliminary report.

The small G protein signaling modulator 3 (SGSM3) has been shown to be associated with small G-protein-coupled receptor signaling. There is little data regarding the impact of SGSM3 polymorphisms on cancer risk. In the present study, we aimed to evaluate the impact of 4-bp insertion/deletion (rs56228771) polymorphism in the 3'UTR of SGSM3 and susceptibility to bladder cancer in a sample of the Iranian population. This case-control study included 143 pathologically confirmed bladder cancer patients and 144 healthy subjects. The SGSM3 4-bp ins/del (rs56228771) variant was determined by mismatch PCR-RFLP. The findings showed that ins/del genotype and ins allele of SGSM3 4-bp ins/del polymorphism significantly increased the risk of bladder cancer (OR = 3.11, 95%CI = 1.70-5.71, P < 0.0001 and OR = 2.11, 95%CI = 1.27-3.52, P = 0.004, respectively). Our findings support an association between 4-bp ins/del polymorphism in the 3'UTR of SGSM3 and the risk of bladder cancer in an Iranian population. Additional studies with larger sample sizes and diverse ethnicities are warranted to establish if such an association exists in general.

Evaluation of transcobalamin II rs1801198 and transcobalamin II receptor rs2336573 gene polymorphisms in recurrent spontaneous abortion.

It has been proposed that transcobalamin 2 (TCN2) and the transcobalamin 2 receptor (TCN2R) are associated with idiopathic recurrent spontaneous abortion (RSA). The aim of the present study was to investigate the impact of TCN2 rs1801198 and TCN2R rs2336573 polymorphism on RSA in a sample of Iranian population. This case-control study was done on 92 RSA patients and 93 normal, fertile women. Genotyping of the TCN2 rs1801198 and TCN2R rs2336573 variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The findings showed no significant association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk/protection of RSA. Our results did not support an association between the TCN2 polymorphism and the risk of RSA in a sample of southeast Iranian population. Larger studies with different ethnicities are needed to evaluate the possible impact of TCN2 and TCN2R polymorphisms on the pathogenesis of RSA. Impact statement What is already known on this subject? Recurrent spontaneous abortion (RSA), a multifactorial condition, is one of the most common complications of pregnancy. It has been proposed that genetic polymorphisms play a role in the pathogenesis of RSA. Few studies have examined the association between TNC2 and TCN2R polymorphisms and the RSA risk and the findings were inconsistent. The aim of the current study was to determine the possible association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the RSA in a sample of the southeast Iranian population. What do the results of the study add? The findings of the present case-control study did not support an association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk of RSA in a sample of the Iranian population. What are the implications of these findings for clinical practice and future research? The findings of this study may provide a basis for future studies with larger sample sizes and different ethnicities on the role of TCN2 and TCN2R polymorphisms in the pathogenesis of RSA.

IKZF1 gene polymorphisms increased the risk of childhood acute lymphoblastic leukemia in an Iranian population.

Genome-wide association studies (GWAS) have proved the association of IKZF1 polymorphisms with childhood acute lymphoblastic leukemia (ALL). In the present study, we aimed to inspect the impact of IKZF1 gene polymorphisms and childhood ALL in a sample of Iranian population who live in south east of Iran. This case-control study was done on 110 children diagnosed with ALL and 120 healthy children. The IKZF1 (rs4132601 T > G, rs11978267 A > G, rs11980379 T > C, and rs10272724 T > C) polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The results showed that rs4132601 T > G polymorphism increased the risk of ALL in the codominant (OR = 2.96, 95 % CI = 1.58-5.54, p = 0.0008, TG vs TT; and OR = 2.75, 95 % CI = 1.31-5.76, p = 0.0094, GG vs TT) and dominant (OR = 2.89, 95 % CI = 1.61-5.19, p = 0.0004, TG + GG vs TT) inheritance models. On the other hand, the rs4132601 G allele increased the risk of ALL (OR = 1.86, 95 % CI = 1.28-2.96; p = 0.0011) in comparison with the T allele. We have also showed that rs11980379 T > C variant increased the risk of ALL in codominant (OR = 2.43, 95 % CI = 1.28-4.60, p = 0.0076, TC vs TT; and OR = 2.35, 95 % CI = 1.14-4.85, p = 0.0291, CC vs TT) and dominant (OR = 2.40, 95 % CI = 1.32-4.36, p = 0.0038, TC + CC vs TT) inheritance models. The rs11980379 C allele increased the risk of ALL (OR = 1.59, 95 % CI = 1.10-2.31, p = 0.0151) compared with T allele. Our study also revealed that the rs10272724 T > C polymorphism increased the risk of ALL in codominant (OR = 2.18, 95 % CI = 1.19-3.99, p = 0.0115, TC vs TT; and OR = 2.67, 95 % CI = 1.24-5.77, p = 0.0131, CC vs TT) and dominant (OR = 2.31, 95 % CI = 1.30-4.08, p = 0.0049, TC + CC vs TT) inheritance models. On the one hand, the rs11980379 C allele increased the risk of ALL (OR = 1.70, 95 % CI = 1.17-2.46, p = 0.0062) compared with T allele, while the rs11978267 A/G polymorphism was not associated with ALL risk. In conclusion, our findings confirm the impact of IKZF1 polymorphisms on childhood ALL risk in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are needed to confirm our findings.

Toll-like Receptor 1 Polymorphisms Increased the Risk of Pulmonary Tuberculosis in an Iranian Population Sample.

A case-control study was carried out that involved 203 individuals diagnosed with pulmonary tuberculosis (PTB) and 203 healthy subjects. Genotyping of TLR1 rs5743551 and rs5743618 polymorphisms was done using polymerase chain reaction-restriction fragments length polymorphism assay. We found that TLR1 rs5743551 variant affected the risk of PTB in the codominant (OR=3.28, 95% CI=1.98-5.45, P<0.0001, GA vs. GG; OR=1.86, 95% CI=1.05-3.28, P=0.033, AA vs. GG) and dominant (OR=2.69, 95% CI=1.67-4.34, P<0.0001, GA+AA vs. GG) inheritance models tested. The A allele was associated with a higher risk of PTB than the G allele (OR=1.33, 95% CI=1.01-1.75, P=0.049). The TG genotype of the rs5743618 variant significantly increased the risk of PTB compared to the risk associated with the TT genotype (OR=3.29, 95% CI=1.82-5.97, P<0.0001). The G allele was associated with a higher risk of PTB than the T allele (OR=3.00, 95% CI=1.69-5.31, P=0.0001). Our findings revealed that TLR1 rs5743551 and rs5743618 polymorphisms affected the risk of PTB in an Iranian population sample. Additional studies with larger sample sizes and involving subjects of different ethnicities are required to validate our present findings.

CCL5 rs2107538 Polymorphism Increased the Risk of Tuberculosis in a Sample of Iranian Population.

Cysteine-cysteine chemokine ligand 5 (CCL5) with immunoregulatory and inflammatory activities has an important role in granuloma formations that activates and stimulates T-cells and macrophages. Cysteine-cysteine chemokine receptor 5 (CCR5) is a chemokine receptor, which is important for migration of immune cells to site of infection. In the present study we investigated the possible association between CCL5 -403G/A (rs2107538), CCL5 -28C/G (rs2280788) and CCR5 Δ32 polymorphisms and pulmonary tuberculosis (PTB) in an Iranian population. This case-control study was performed on 160 patients with pulmonary tuberculosis and 160 unrelated healthy subjects. The CCL5 -403G/A, CCL5 -28C/G and CCR5 Δ32 polymorphisms were genotyped by allele-specific polymerase chain reaction (AS-PCR), tetra amplification refractory mutation system polymerase chain reaction (T-ARMS PCR) and PCR, respectively. Our results showed that GA as well as GA+AA genotypes of CCL5 -403G/A (rs2107538) increased the risk of PTB in comparison with GG genotype (OR=1.70, 95% CI=1.03-2.81, P=0.038 and OR=1.64, 95% CI=1.00-2.68, P=0.049, respectively). No significant association was found between CCL5 -28C/G as well as CCR5 Δ32 polymorphism and PTB risk. In conclusion, our findings proposed that CCL5 -403G>A polymorphism may be a risk factor for susceptibility to PTB in our population. Larger sample sizes with different ethnicities are required to validate our findings.

Association of functional polymorphism at the miR-502-binding site in the 3' untranslated region of the SETD8 gene with risk of childhood acute lymphoblastic leukemia, a preliminary report.

MicroRNAs (miRNAs), a class of non-coding RNAs, bind to the 3' untranslated regions (UTRs) of mRNAs, where they interfere with translation of genes and are implicated in the pathogenesis of diverse diseases. In the present study, we evaluate the impact of rs16917496 polymorphism within the miR-502 miRNA seed region at the 3'UTR of SEDT8 on childhood acute lymphoblastic leukemia (ALL). This case-control study was done on 75 ALL and 115 healthy children. Genotyping of rs16917496 C/T polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that CT as well as CT + TT decreased the risk of ALL in comparison with CC genotype (odds ratio (OR) = 0.29, 95 % confidence intervals (95 % CI) = 0.11-0.78, P = 0.014 and OR = 0.31, 95 % CI = 0.12-0.82, P = 0.016, respectively). Our results demonstrated that SETD8 rs16917496 C/T polymorphism was associated with decreased risk of developing pediatric ALL in Zahedan, southeast Iran. Larger studies with different ethnicities are desired to validate our findings.

CXC chemokines CXCL1, CXCL9, CXCL10 and CXCL12 are variably expressed in patients with sickle cell disease and carriers: are they predictive tools for disease complications?

BACKGROUND: Sickle cell hemoglobinopathies are amongst a group of genetic disorders resulting from a single base-pair DNA mutation at the beta chain of hemoglobin. Chemokines and cytokines play a part in the pathogenesis of inflammatory and infectious diseases. They are also involved in balancing angiogenesis/angiostasis processes to form new vascular networks. We aimed the present study to measure the circulating CXC chemokines CXCL1, CXCL9, CXCL10, and CXCL12 in the plasma of sickle cell patients (SCD). METHODS: This cross-sectional study was conducted at the Kerman Special Disease Center and Rafsanjan Molecular Medicine Research Center during 2010 to 2011. Peripheral blood specimens were collected from 77 children with SCD and 70 controls. Serum samples were isolated and CXCL1, CXCL9, CXCL10, and CXCL12 were measured using ELISA. RESULTS: The findings of this study demonstrated that serum concentrations of CXCL1 and CXCL12 were elevated in SCD patients when compared with controls. Results also showed that the circulating levels of CXCL9 and CXCL10 were decreased in SCD patients in comparison to control subjects. However, we found increased levels of CXC chemokines in SCD patients suffering from pain crisis but the difference was not significant. CONCLUSIONS: According to the results of this study it can probably be concluded that the balance between angiogenesis/angiostasis CXC chemokines is an important predictive factor for initiation of complications in SCD patients. The elevated level of pro-inflammatory CXC chemokines may also be related to inflammatory responses associated with SCD complication.

The comparison of pain caused by suprapubic aspiration and transurethral catheterization methods for sterile urine collection in neonates: a randomized controlled study.

This study was performed to compare the levels of pain experienced by young infants undergoing either suprapubic aspiration (SPA) or transurethral catheterization (TUC) for the collection of sterile urine samples. This prospective randomized clinical trial was conducted in hospitalized neonates in a university-affiliated hospital. Patients who required urine cultures were randomly assigned into one of two groups, the SPA or TUC group. The infants' faces were videotaped, and the changes in the facial expression and physiological parameters during the procedure were scored using the Premature Infant Pain Profile (PIPP) in a blind manner. The primary outcome was the severity of the pain experienced during each procedure, and the secondary outcomes were the success rate, the duration, and the complications of each procedure. Ninety-four percent of male infants in the TUC group and 77.3% in the SPA group were uncircumcised (P = 0.1). The mean (SD) of the PIPP pain scores did not differ between groups (9.95 ± 3.7 in SPA and 9.64 ± 3.2 in TUC, P = 0.6). The duration of TUC was longer. Both methods can be used to collect urine from neonates, but the difficulty of performing TUC on females and uncircumcised males should be considered.

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.

Association between Mir-499, Mir-27a, and Mir-146a polymorphisms and their susceptibility to recurrent spontaneous abortion; in silico analysis.

Objective: Recurrent spontaneous abortion (RSA) is defined as two or more pregnancy losses before 24 gestational weeks, accounting for 1-3% of fertile couples. A vast majority of single-nucleotide polymorphisms (SNPs) in some microRNA (miRNA) genes can change the miRNA-mRNA interaction and are associated with the risk of RSA. This study was designed to better elucidate the association between miR-27a, miR-499, and miR-146a polymorphisms and RSA risk. Materials and Methods: SNP genotyping of miR-27a (rs895819), miR-499 (rs3746444), and miR-146a (rs2910164) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra amplification-refractory mutation system PCR in 98 patients with RSA and 105 healthy subjects. Results: Our results showed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were significantly associated with RSA risk, whereas no significant differences were observed between the rs2910164 polymorphism and RSA susceptibility. Conclusion: We proposed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were correlated with RSA in our population, but the miR-146a rs2910164 variant was not associated with the risk of RSA.

Association between CDH1 and MSX1 gene polymorphisms and the risk of nonsyndromic cleft lip and/or cleft palate in a southeast Iranian population.

Objective : Orofacial clefts such as cleft palate (CP) and cleft lip (CL) and/or cleft palate (CL/P) are the most common congenital anomalies of the head and neck. The aims of the present study were to evaluate the possible association between CDH1 (rs11642413 and rs16260) and MSX1 (rs12532 and rs3775261) gene polymorphisms and nonsyndromic cleft lip and/or cleft palate (NS-CL/P) in a sample of the Iranian population. Design and Setting : This case-control study was performed on 100 subjects with NS-CL/P and 100 healthy unrelated control subjects. Tetra amplification refractory mutation system-polymerase chain reaction and multiplex polymerase chain reaction were used to detect the single-nucleotide polymorphisms. Results : There was a significant difference between NS-CL/P subjects and control subjects regarding CDH1 rs16260 C > A polymorphism, and the rs16260 AC as well as the rs16260 AA genotypes were associated with NS-CL/P susceptibility (odds ratio [OR] = 3.02, 95% confidence interval [CI] =1.51-6.00, P = .001; and OR = 8.05, 95% CI = 1.72-37.75, P = .002, respectively). No significant difference was found between the groups regarding CDH1 rs11642413 polymorphism. Although MSX1 rs3775261 polymorphism was not a risk factor for the disease, the rs12532 AG and rs12532 GG genotypes were associated with NS-CL/P risk (OR = 2.82, 95% CI = 1.55-5.15, P = .001; and OR = 8.42, 95% CI = 2.26-31.29, P = .004, respectively). Conclusion : Our data suggest that CDH1 and MSX1 gene polymorphisms are risk factors for susceptibility to NS-CL/P in a sample of the Iranian population. Larger studies are required to validate our findings.

Association of LIN28B Gene Polymorphisms (rs221634, rs221635, rs314276, rs9404590, and rs12194974) with Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.

BACKGROUND AND AIM: Lymphoma is a common hematopoietic cancer.  It has been proposed that LIN28B gene and its variations may have function in cancer progression and metastasis. Therefore, the purpose of this investigation has been to examine the correlation among LIN28B gene polymorphisms (such as rs221634 A>T, rs221635 T> C, rs314276 C>A, rs9404590 T>G, and rs12194974 G>A) as well as the risk of NHL in an Iranian sample. MATERIALS AND METHODS: In the current case-control research, 175 individuals with Non-Hodgkin Lymphoma along with 175 normal controls participated; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology has been utilized to the genotype samples. RESULTS: Our data demonstrated that rs12194974 and the rs221635 variants have been correlated with higher NHL risk, while rs221634 and rs314276 variants were correlated with lower risk of NHL (P≤0.05). In addition, we detected an association between rs221634 and treatment with R-CHOP. No substantial correlation has discovered among rs9404590 polymorphism and NHL in any inheritance models (P≥0.05). CONCLUSION: This was the first investigation evaluating the correlation among LIN28B gene polymorphisms as well as the occurrence of NLH. Further studies in different ethnic populations and large-scale sample size are needed to support results.

The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case-Control Study with Bioinformatics Analysis.

Breast cancer (BC) is a complex disease caused by molecular events that disrupt cellular survival and death. Discovering novel biomarkers is still required to better understand and treat BC. The reticulon-4 (RTN4) gene, encoding Nogo proteins, plays a critical role in apoptosis and cancer development, with genetic variations affecting its function. We investigated the rs34917480 in RTN4 and its association with BC risk in an Iranian population sample. We also predicted the rs34917480 effect on RTN4 mRNA structure and explored the RTN4's protein-protein interaction network (PPIN) and related pathways. In this case-control study, 437 women (212 BC and 225 healthy) were recruited. The rs34917480 was genotyped using AS-PCR, mRNA secondary structure was predicted with RNAfold, and PPIN was constructed using the STRING database. Our findings revealed that this variant was associated with a decreased risk of BC in heterozygous (p = 0.012), dominant (p = 0.015), over-dominant (p = 0.017), and allelic (p = 0.035) models. Our prediction model showed that this variant could modify RTN4's mRNA thermodynamics and potentially its translation. RTN4's PPIN also revealed a strong association with apoptosis regulation and key signaling pathways highly implicated in BC. Consequently, our findings, for the first time, demonstrate that rs34917480 could be a protective factor against BC in our cohort, probably via preceding mechanisms.