Association analysis of rs1049255 and rs4673 transitions in p22phox gene with coronary artery disease: A case-control study and a computational analysis

Background The p22phox gene encodes the main subunit of NADH/NADPH-oxidase. This enzyme is expressed in smooth muscle cells of arteries, and it produces the reactive oxygen species. On the other hand, oxidative stress plays a main role in the pathogenesis of coronary artery disease (CAD). Aim The aim of this study is to evaluate the association between rs4673 and rs1049255 polymorphisms of p22phox gene with CAD in an Iranian population which was followed with a computational analysis approach. Methods In a cross-sectional study, we collected blood samples of 302 Iranian Caucasian including 143 patients and 159 healthy controls. Genotype of the polymorphisms was detected through PCR-RFLP method. A computational analysis was also performed using SNAP, Polyphen-2, Chou-Fasman, RNAsnp, and miRNA SNP databases. Results Data of case control study demonstrated that CT genotype (R = 1.84, 95% CI = 1.13–3.00, p = 0.014) and T allele (OR = 1.53, 95% CI = 1.09–2.15, p = 0.013) of rs4673 polymorphism, have a significant association with enhanced risk of CAD. But rs1049255 analysis demonstrated the absence of such an association with CAD. Indeed, in silico data analysis demonstrated that rs4673 transition could impact on function of p22phox protein (SNAP score 56, expected accuracy 75%; Polyphen-2 score 0.99, sensitivity 0.09, specificity 0.99). Data derived from miRNA SNP database demonstrated that rs1049255 polymorphism increases the affinity of attachment between has-miR-3689a-3b with 3′-UTR of p22phox gene. Conclusion Our data demonstrated that rs4673 transition may be involved in susceptibility to CAD and could be applied as a potential biomarker for this disease

The effect of parental medical history on the prevalence of cerebrovascular diseases in their children in an Iran IAN population

Introduction: still a controversial issue, family history is known as a risk factor for the development of Cerebrovascular Diseases (CVD). In this study, we aimed to evaluate the relationship between parental history and risk of CVD in their offspring in Iranian population. Methods: Isfahan Cohort Study (ICS) included total 6504 healthy participants which were randomly selected through a two-stage cluster sampling method from three districts. The participants were followed prospectively for 10 years. The diagnosis of CVD were confirmed by expert panelist. Clinically validated history of CVD was established for definition of parental history of CVD. Types of history were categorized into paternal, maternal, both parents, and no history. Results: The prevalence of CVD is generally higher among female offspring compared with male ones (P<0.001). The relative risk of CVD with maternal history was not significant (95CI=0.95-2.29). By adjusted model analysis, history of CVD in both parents affected the risk of CVD in their male children (RR=2.13, P=0.033, 95CI). By crude model analysis, maternal history of CVD (P=0.047), history of CVD in both parents (P=0.032), and maternal history of hypertension (P=0.005) were determined as risk factors of CVD in offspring. Indeed, the mean age of CVD in offspring decreases based on this order: history of hypertension in parents, paternal history of CVD in both parents, maternal history of CVD, and no history (P<0.001). Conclusion: Early and regular screening for CVD development is necessary in female offspring of the families with the present history of CVD from maternal side. This group are at risk and should be considered as the target group for screening and taking preventive measures. © 2018 Iran University of Medical Sciences. All rights reserved

The impact of third party reproduction on family and kinship

The development of in vitro fertilization (IVF) in the UK, in 1978, proved a major breakthrough in the process of human reproduction, which had remained constant in human history. The impact of IVF and the ensuing assisted reproductive technologies (ARTs) has not been limited in revolutionizing the "natural" practice of biological reproduction, but has reached out to and affected almost every institution in society. Family and kinship, as the social expression of reproduction and the institutions which are the most transparently structured realm of human life are those most profoundly affected by ARTs. Although literature on the implications of ARTs is in general abundant, this article presents new insights on their impact on family and kinship in Iran, which remains a unique case in the Muslim world. It explores the particular way ARTs, especially third-party donation, have been endorsed and practiced in Iran, and their consequences for the family, the infertile individuals, and their position vis-à -vis their kin and social group. The conclusion points to the lack of clarity concerning the initial rulings by the Islamic jurists, who allowed the practice of ARTs, and which has led to a number of unintended consequences regarding the legal, religious, cultural, and ethical issues, affecting the family, its structure and the relationship between the kin group. These consequences range, inter alia, from the question of the anonymity of third-party donor, to the permissibility of gamete donation between blood relatives, and to the absence of enforceable legislation. © 2021 Avicenna Research Institute. All rights reserved

Wilms tumour

Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and evaluation of newer surgical procedures are key areas for future research

Association between (GT)n repeats in heme oxygenase-1 gene promoter and 3-year survival of patients with acute leukemia: A controlled, cross-sectional study

Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance is remained as the most problematic issue. It is hypothesized that the HO-1 gene up-regulation is responsible for tumor resistance to chemotherapy or radiotherapy-induced apoptosis. HO-1 expression levels are related to (GT)n microsatellite polymorphisms in the location of its promoter.This study designed to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene between acute leukemia patients and healthy controls. Indeed, 3-year disease-free survival was also evaluated. Materials and Methods: Sixty-three patients with acute leukemia and 70 healthy infants were included in this study. We used patient�s medical records to collect data about survival after chemotherapy. The number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer. Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in both cases and controls. Children with longer alleles ((GT)n � 27) had enhanced 3-year survival rate after treatment with chemotherapy or radiotherapy (P&lt;0.05). Conclusion: Although no significant differences were observed between leukemia patients and controls regarding allelic frequency, we found elevated frequency of �LL� genotype in leukemia patients with good prognosis and 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

Association between (GT)n repeats in heme oxygenase-1 gene promoter and 3-year survival of patients with acute leukemia: A controlled, cross-sectional study

Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance is remained as the most problematic issue. It is hypothesized that the HO-1 gene up-regulation is responsible for tumor resistance to chemotherapy or radiotherapy-induced apoptosis. HO-1 expression levels are related to (GT)n microsatellite polymorphisms in the location of its promoter.This study designed to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene between acute leukemia patients and healthy controls. Indeed, 3-year disease-free survival was also evaluated. Materials and Methods: Sixty-three patients with acute leukemia and 70 healthy infants were included in this study. We used patient�s medical records to collect data about survival after chemotherapy. The number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer. Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in both cases and controls. Children with longer alleles ((GT)n � 27) had enhanced 3-year survival rate after treatment with chemotherapy or radiotherapy (P&lt;0.05). Conclusion: Although no significant differences were observed between leukemia patients and controls regarding allelic frequency, we found elevated frequency of �LL� genotype in leukemia patients with good prognosis and 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

Association between (GT)n repeats in heme oxygenase-1 gene promoter and 3-year survival of patients with acute leukemia: A controlled, cross-sectional study

Background: Acute leukemia is a common pediatric cancer. Novel strategies for treatment of acute leukemia have been developed, but treatment resistance is remained as the most problematic issue. It is hypothesized that the HO-1 gene up-regulation is responsible for tumor resistance to chemotherapy or radiotherapy-induced apoptosis. HO-1 expression levels are related to (GT)n microsatellite polymorphisms in the location of its promoter.This study designed to compare allelic frequencies of (GT)n microsatellite polymorphisms in HO-1 gene between acute leukemia patients and healthy controls. Indeed, 3-year disease-free survival was also evaluated. Materials and Methods: Sixty-three patients with acute leukemia and 70 healthy infants were included in this study. We used patient�s medical records to collect data about survival after chemotherapy. The number of GT repeats in HO-1 promoter was determined by an ABI 3100 sequencer. Results: The HO-1 GT repeats ranged from 14 to 34 with peaks at 27 repeats in both cases and controls. Children with longer alleles ((GT)n � 27) had enhanced 3-year survival rate after treatment with chemotherapy or radiotherapy (P&lt;0.05). Conclusion: Although no significant differences were observed between leukemia patients and controls regarding allelic frequency, we found elevated frequency of �LL� genotype in leukemia patients with good prognosis and 3-year surveillance. Radiotherapy and chemotherapy might elevate the expression levels of HO-1 with subsequent increased resistance of leukemia patients to therapy. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

J. Med. Genet.

Background: Primary microcephaly (MCPH) is a genetically heterogeneous disorder showing an autosomal recessive mode of inheritance. Affected individuals present with head circumferences more than three SDs below the age- and sex-matched population mean, associated with mild to severe mental retardation. Five genes (MCPH1, CDK5RAP2, ASPM, CENPJ, STIL) and two genomic loci, MCPH2 and MCPH4, have been identified so far. Methods and results: In this study, we investigated all seven MCPH loci in patients with primary microcephaly from 112 Consanguineous Iranian families. In addition to a thorough clinical characterisation, karyotype analyses were performed for all patients. For Homozygosity mapping, microsatellite markers were selected for each locus and used for genotyping. Our investigation enabled us to detect homozygosity at MCPH1 (Microcephalin) in eight families, at MCPH5 (ASPM) in thirtheen families. Three families showed homozygosity at MCPH2 and five at MCPH6 (CENPJ), and two families were linked to MCPH7 (STIL). The remaining 81 families were not linked to any of the seven known loci. Subsequent sequencing revealed eight, 10 and one novel mutations in Microcephalin, ASPM and CENPJ, respectively. In some families, additional features such as short stature, seizures or congenital hearing loss were observed in the microcephalic patient, which widens the spectrum of clinical manifestations of mutations in known microcephaly genes. Conclusion: Our results show that the molecular basis of microcephaly is heterogeneous; thus, the Iranian population may provide a unique source for the identification of further genes underlying this disorder