Epistatic interaction between adiponectin and survivin gene polymorphisms in endometrial carcinoma

Adiponectin appears to play an important role in the development and progression of several obesity-related malignancies. Also, overexpression of survivin, an inhibitor of apoptosis protein, is associated with increased risk of cancers. The aim of this study was to investigate the association between two polymorphisms in the adiponectin gene and endometrial cancer (EC) risk. We also investigated whether epistasis between surviving and adiponectin gene polymorphisms are associated with EC risk in an Iranian population.The samples comprised formalin-fixed, paraffin-embedded tissue sections obtained from the archive of the pathology department, Imam-Khomeini Hospital and Firouzgar hospital. After DNA extraction the genotyping was performed using PCR-RFLP technique.Single nucleotide polymorphisms (SNPs) in adiponectin (rs1063539, rs2241766) and survivin (rs9904341) gene were evaluated in the study. The increased frequency of ADIPOQ rs1063539C allele (CC. +. CG genotype) was associated with decreased EC risk OR: 0.39(0.17-0.90). Survivin rs9904341C allele (CC. +. CG genotype) was associated with increased EC risk crude OR: 2.75(1.27-5.95), adjusted OR: 2.93(1.27-6.76). We observed an epistatic interaction between survivin rs9904341 CC. +. CG genotype and ADIPOQ rs1063539 GG genotype increasing the risk of EC compared to those with other genotypes OR: 4.86(1.88-12.54), P=0.001.Our findings indicate that adiponectin might have a modulatory effect on survivin role and function in EC, which requires further investigation. © 2014 Elsevier GmbH

Adverse reactions following immunization with MMR vaccine in children at selected provinces of Iran

Background: Several adverse events following immunization (AEFI) have been attributed to immunization with live attenuated measles, mumps, and rubella (MMR) vaccines. The MMR vaccine was introduced into the routine infant immunization schedule in 2003, followed by a second dose of vaccine at school-entry for children 4 to 6 years of age. The objective of this study was to characterize adverse reactions following MMR vaccination in Iran. Methods: Children who received the MMR vaccine and resided in five selected provinces of Iran were examined weekly for four weeks to detect well-known AEFIs that included: parotitis, fever and convulsions, convulsions without fever, encephalopathy, and anaphylactic reactions. Incidence of AEFIs were calculated and compared among recipients in both age groups. Results: During the follow-up period, trained providers reported 792 AEFIs. Parotitis was the most frequent event occurring in 1.8 of recipients. Of 14,109 children vaccinated at 12 months of age the following AEFIs occurred: parotitis (147), fever and convulsions (8), convulsions (7), encephalopathy (1), and anaphylactic reactions (1). Of 29,338 children vaccinated at 4 to 6 years of age, parotitis, fever and convulsions, encephalopathy, and anaphylaxis occurred in 626, 5, 1, and 1 child, respectively; no convulsions without fever were reported in this age group. Conclusion: Parotitis is the most frequent AEFI among MMR vaccine recipients in Iran. Incidence rates of AEFIs following MMR vaccination in Iran are similar to rates of AEFIs reported in other studies

Association of vascular endothelial growth factor (VEGF) Gene polymorphisms and expression with the risk of endometriosis: a case�control study

Endometriosis is a polygenic and multifactorial gynecology situation which might be associated with angiogenesis. In the current study we assess the role of vascular endothelial growth factor (VEGF) � 2578 A/C, and + 936 C/T polymorphisms in susceptibility to endometriosis and checking the expression of VEGF mRNA in eutopic tissue of endometrium with and without endometriosis. The study was comprised of 300 patients who underwent laparascopic or laparotomy surgery with 100 cases who had confirmed histological diagnosis of endometriosis, and 200 controls with no histological diagnosis of disease. The genotyping of VEGF polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism (PCR�RFLP) technique and the gene expression in tissue was determined using Real-Time PCR assay. There was no important difference of allele distribution of the � 2578 A/C (P = 0.7) and + 936 C/T (P = 0.5) polymorphisms among endometriosis cases and controls. Study of VEGF expression during the menstrual cycle, showed that endometrial tissue in cases group expressed more VEGF mRNA at the secretory phase compared to the proliferative phase (P = 0.03). Our results suggest that � 2578 A/C and + 936 C/T polymorphisms of VEGF did not seem to have impact on endometriosis predisposition in our study population. Also we did not find any link between VEGF mRNA expression and risk of endometriosis. © 2019, Springer Nature B.V

Sex-dependent association of ACE (I/D) polymorphism with Meniere's disease

Background: Meniere's disease is an inner ear disorder presenting with recurrent episodic vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural fullness as its main symptoms. Previous studies have demonstrated the role of blood pressure in Meniere's disease. The purpose of this study was to determine the role of ACE, rs4646994 I/D polymorphism in Meniere's disease. Methods and materials: In this case-control study, 67 individuals with Meniere's disease and 100 healthy individuals as a control group were enrolled. Patients DNA samples were extracted from the blood by the phenol-chloroform method. The frequency of genotypes were determined by polymerase chain reaction (PCR) technique. Results: The genotypes and allele frequencies were not significantly different between the studied populations (p >.05). There was significant differences for distribution of I/D genotype between females and males (p <.05). The patients with I/D genotype also showed significant difference in the level of hearing (p <.05). Conclusions: This study demonstrates the gender association of ACE rs4646994 polymorphism with Meniere's disease in an Iranian population. © 2020 Elsevier B.V

Investigating the association of matrix metalloproteinase-2 gene variants with endometriosis in an Iranian population

Objectives: matrix metalloproteinases including matrix metalloproteinase-2 play a key role in endometrial extra cellular matrix breakdown in endometriosis. Aberrant expression of matrix metalloproteinase-2 has been reported in eutopic and ectopic endometrial tissue of endometriosis patients so altered expression of matrix metalloproteinase-2 due to polymorphisms may lead to establishment and progression of endometriosis. In this study the association between -735 C/T (rs2285053) and â��1575 G/A (rs243866) variants of matrix metalloproteinase-2 gene with presence of endometriosis in an Iranian population were investigated for the first time. Study design: A case-control association study was conducted to investigate the role of MMP-2â��735 C/T and ₁₅₇₅ G/A variants in development of endometriosis. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine genotype frequencies of these variants in 100 endometriosis patients and 200 normal samples. Total genomic DNA was extracted from blood samples and single-nucleotide polymorphism flanking regions were amplified using designed specific primers. Enzymatic digestion was performed using Pag I and Hinf I restriction enzymes for rs2285053 and rs243866 variants, respectively. Statistical analysis was ascertained using statistical package for social science version 16 and â��SHEsisâ�� software. Results: There were no significant differences in genotype frequencies of rs2285035 (-735C/T) variant between case and control groups (CC + CT vs. TT p = 0.40; OR = 0.50, 95 CI 0.100â��2.551). There were also no significant differences for C allele frequencies in both case and control groups (p = 0.9). For variant rs243866 (â��1575 G/A) the differences in genotype frequencies between case and controls group were determined to be significant (GG + GA vs. AA p = 0.041; OR = 6.46, 95 CI 0.82â��50.43). The frequency of G allele was significantly different in case and control groups (p = 0.037). Conclusion: In conclusion, existence of rs243866 variant in promoter region of matrix metalloproteinase-2 gene can increase the risk of endometriosis in Iranian women. © 202

A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes

Objective: Wolcott-Rallison syndrome (WRS) is an extremely rare autosomal recessive condition, characterized by permanent neonatal diabetes mellitus (PNDM) associated with skeletal dysplasia, growth retardation and liver dysfunction. WRS is caused by biallelic mutations in the gene encoding eukaryotic translation initiation factor 2alpha kinase 3 (EIF2AK3). Methods: As part of a comprehensive study on clinical and genetic investigation of neonatal diabetes in an Iranian population, 60 unrelated Iranian subjects referred with PNDM were analyzed. All the probands were screened for KCNJ11, INS, ABCC8 and EIF2AK3 using a polymerase chain reaction�based sequencing approach. Results: We identified 9 different variants in EIF2AK3 in 11 unrelated Iranian probands, of which 5 variants were shown to be novel and not reported previously. The diagnosis of WRS was made by molecular genetic testing and confirmed by clinical re-evaluation of the subjects. Clinical follow up of the affected individuals shows that in at least some of them, PNDM was associated with short stature, failure to thrive, neurodevelopmental delay, epilepsy and hepatic and renal dysfunction. There was a strong family history of neonatal diabetes in the families of the probands with a high mortality rate. Conclusion: WRS is a common cause of PNDM in children of consanguineous parents. Furthermore, clinical diagnosis of WRS would have been delayed or possibly missed without genetic testing because this study shows that the associated features of WRS might be obscured by a diagnosis of PNDM. Therefore EIF2AK3 should be considered for any infant and young child with PNDM, particularly if the parents are related. © 2017 Diabetes Canad

A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes

Objective: Wolcott-Rallison syndrome (WRS) is an extremely rare autosomal recessive condition, characterized by permanent neonatal diabetes mellitus (PNDM) associated with skeletal dysplasia, growth retardation and liver dysfunction. WRS is caused by biallelic mutations in the gene encoding eukaryotic translation initiation factor 2alpha kinase 3 (EIF2AK3). Methods: As part of a comprehensive study on clinical and genetic investigation of neonatal diabetes in an Iranian population, 60 unrelated Iranian subjects referred with PNDM were analyzed. All the probands were screened for KCNJ11, INS, ABCC8 and EIF2AK3 using a polymerase chain reaction�based sequencing approach. Results: We identified 9 different variants in EIF2AK3 in 11 unrelated Iranian probands, of which 5 variants were shown to be novel and not reported previously. The diagnosis of WRS was made by molecular genetic testing and confirmed by clinical re-evaluation of the subjects. Clinical follow up of the affected individuals shows that in at least some of them, PNDM was associated with short stature, failure to thrive, neurodevelopmental delay, epilepsy and hepatic and renal dysfunction. There was a strong family history of neonatal diabetes in the families of the probands with a high mortality rate. Conclusion: WRS is a common cause of PNDM in children of consanguineous parents. Furthermore, clinical diagnosis of WRS would have been delayed or possibly missed without genetic testing because this study shows that the associated features of WRS might be obscured by a diagnosis of PNDM. Therefore EIF2AK3 should be considered for any infant and young child with PNDM, particularly if the parents are related. © 2017 Diabetes Canad