The Association Between Genetic Variants in ACE1and ACE2 Genes with Susceptibility to COVID-19 Infection.

Angiotensin-converting enzyme 2 (ACE2) receptors facilitate the entry of the causative virus severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) into target cells. Some ACE gene variants have been suggested to be involved in COVID-19 pathogenesis. So, the aim was to assess the association between ACE1 rs4646994 and ACE2 rs2285666 genes polymorphisms and the susceptibility and severity of COVID-19. This case-control study was conducted on 197 patients with COVID-19 and 197 healthy controls. ACE-1 insertion/deletion (I/D) (rs4646994) and ACE2 rs2285666 genes polymorphisms were determined by the amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) technique. The DD genotype of ACE1 I/D polymorphism was associated with increased susceptibility to COVID-19 infection (p = 0.012), whereas the ID genotype of this polymorphism was associated with decreased susceptibility (p = 0.003) (significance level = 0.017). There was no significant association in allele and genotype distribution of ACE2 rs2285666 polymorphism between cases and controls. The ACE1 I/D polymorphism may be considered as a risk factor for COVID-19 susceptibility.

Association of Genotypes of ANGPTL3 with Vitamin D and Calcium Concentration in Cardiovascular Disease.

One of the leading causes of mortality worldwide is cardiovascular disease, which is influenced by some variables, including calcium and vitamin D. This study aimed to assess the relationship between Angiopoietin-Like 3 (ANGPTL3) gene polymorphisms with vitamin D and calcium levels in cardiovascular disease (CVD) patients. In this research, 1002 people participated. Participants' anthropometric parameters, and FBG, calcium, and vitamin D were assessed. Blood samples were used to extract DNA. Taqman®-based polymerase chain reaction (PCR) was used to conduct genetic analysis for the rs10789117 and rs17458195. Statistical analysis was applied to determine differences across subgroups and the relationship between polymorphisms and disease. Age, body mass index (BMI), fasting Blood Sugar (FBG), phenylalanine ammonia-lyase (PAL), and smoking history were significantly correlated with CVD. Vitamin D was statistically associated with rs10789117 and rs17458195 in non-CVD individuals. In the moderate group, individuals with the C allele in rs10789117 showed a tenfold increase in vitamin D deficiency compared to those with the A allele. However, in rs11207997, individuals with the T allele had 5 to 6 times higher vitamin D deficiency than those with the C allele in all groups. This research demonstrates the relationship between some ANGPTL3 gene polymorphisms and complement levels in CVD patients. It may be concluded that individuals carrying these variants would likely benefit from using vitamin D and calcium supplements to avoid CVD.

The Association Between rs1748195 and rs11207997 Variants of the ANGPTL3 Gene and Susceptibility to Cardiovascular Disease in the MASHAD Cohort Study.

There is a strong genetic predisposition to cardiovascular disease (CVD). Loss-of-function variants of the angiopoietin-like 3 (ANGPTL3) gene have been reported to be associated with several lipid-related CVD risk factors that include serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) level, and total cholesterol (TC). We aimed to determine the association of two genetic variants, rs1748195 and rs11207997, of the ANGPTL3 locus and CVD risk in the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. The participants were 1002 individuals in the MASHAD cohort, with or without CVD, during the 6 years of follow-up. The subjects were categorized into two groups according to serum HDL concentration. DNA was extracted by the routine salting-out method, and genotyping of rs1748195 and rs11207997 variants of the ANGPTL3 gene was performed using the ARMS PCR method. Univariate and multivariate statistical analysis was used to assess the two gene variants' association with incident CVD and baseline lipid profile. There was a significant relationship between rs1748195 GG genotype and CVD risk in the individuals with a normal serum HDL-C. There was a significant association between the CT genotype of the rs11207997 polymorphism and CVD risk in individuals with a low serum HDL-C. Furthermore, carriers of the GG genotype of the rs1748195 and CT genotype of rs11207997 variant of ANGPTL3 had a higher risk of developing CVD disease. We have shown that the 1748195(GG) and 11207997(CT) gene variants of the ANGPTL3 locus are associated with an increased risk of CVD in an Iranian population sample.

Clinical Manifestations Associated with the Domain-Containing Protein 2 Gene Mutation in an Iranian Family with Spastic Paraplegia 54.

INTRODUCTION: Spastic paraplegia type 54 (SPG54) is an autosomal recessive disorder caused by bi-allelic mutations in the DDHD-domain-containing protein 2 (DDHD2) gene. Worldwide, over 24 SPG54 families and 24 pathogenic variants have been reported. Our study aimed to describe the clinical and molecular findings of a pediatric patient from a consanguineous Iranian family with significant motor development delay, walking problems, paraplegia, and optic atrophy. METHODS: The patient was a 7-year-old boy with severe neurodevelopmental and psychomotor problems. Neurological examinations, laboratory tests, electroencephalography, computed tomography scan, and brain magnetic resonance scan (MRI) were carried out for clinical evaluation. Whole-exome sequencing and in silico analysis were undertaken to identify the genetic cause of the disorder. RESULTS: The neurological examination showed developmental delay, spasticity in the lower extremities, ataxia, foot contractures, and deep tendon reflexes in the extremities. The computed tomography scan was normal, but MRI revealed corpus callosum thinning with atrophic changes in the white matter. The genetic study reported a homozygous variant (c.856 C>T, p.Gln286Ter) in the DDHD2 gene. The homozygous state was confirmed by direct sequencing in the proband and his 5-year-old brother. This variant was not reported as a pathogenic variant in the literature or genetic databases and was predicted to affect the function of the DDHD2 protein. CONCLUSION: The clinical symptoms in our cases were similar to the previously reported phenotype of SPG54. Our results deepen the molecular and clinical spectrum of SPG54 to facilitate future diagnoses.

Treatment with Hydroxyurea Leads to Fetal Hemoglobin Reactivation through CA1 and LIN28B Genes: An In Vitro Study.

Hydroxyurea (HU) is an effective drug to increase fetal γ-globin gene (Hb F) expression, replacing the missing adult ß-globin gene. The mechanism of Hb F induction by HU and improvement in clinical symptoms are still poorly understood. The current study aimed to improve the molecular understanding of drug-induced alterations and reveals genes related to HU treatment responsiveness in ß-thalassemia (ß-thal). We analyzed the GSE109186 dataset using system biology and weighted gene coexpression network analysis (WGCNA) to identify and quantify gene expression changes reflected in the HU-treated human erythroblastic leukemia cells. The K562 cell line was treated in 50, 100, and 150 µM concentrations of HU for 24, 48, and 72 hours with three replications. The alteration of CA1, LIN28B and Hb F gene expression in HU-treated cells was evaluated using the real-time polymerase chain (real-time PCR) technique. The results showed that LIN28B has an increase of 4.27-fold on the first day of HU-treatment in 50 µM (p < 0.01). The CA1 expression showed a decrease at all times and doses of treatment, and the most decrease happened in 48 hours and 50 µM (p < 0.04). Hb F also showed the highest increase in 100 µM after 24 hours of treatment (5.18-fold). In summary, the data suggest that alteration of LIN28B and CA1 gene expression is associated with γ-globin increasing in HU-treated cells.

The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: an experimental study.

BACKGROUND: Tramadol is a widely used synthetic opioid. Substantial research has previously focused on the neurological effects of this drug, while the efficacy of various treatments to reduce the associated side effects has not been well studied. This study aimed to evaluate the protective effects of naloxone, diazepam, and quercetin on tramadol overdose-induced seizure and sedation level in male rats. METHODS: The project was performed with 72 male Wistar rats with an average weight of 200-250 g. The rats were randomly assigned to eight groups. Tramadol was administered intraperitoneally at an initial dose of 25 mg/kg/day. On the 14th day, tramadol was injected at 75 mg/kg, either alone or together with naloxone, diazepam, and quercetin (acute and chronic) individually or in combination. The rats were monitored for 6 h on the last day, and the number, the duration, and the severity of seizures (using the criteria of Racine) were measured over a 6-h observation period. The sedation level was also assessed based on a 4-point criterion, ranging from 0 to 3. Data were analyzed in SPSS software using Kruskal-Wallis, Chi-square, regression analysis, and generalized estimating equation (GEE) tests. The significance level was set at P < 0.05. RESULTS: The naloxone-diazepam combination reduced the number, severity, and cumulative duration of seizures compared to tramadol use alone and reduced the number of higher-intensity seizures (level 3, 4) to a greater extent than other treatments. Naloxone alone reduced the number and duration of seizures but increased the number of mild seizures (level 2). Diazepam decreased the severity and duration of seizures. However, it increased the number of mild seizures (level 2). In comparison with the tramadol alone group, the acute quercetin group exhibited higher numbers of mild (level 2) and moderate (level 3) seizures. Chronic quercetin administration significantly increased the number of mild seizures. In the GEE model, all groups had higher sedation levels than the saline only group (P < 0.001). None of the protocols had a significant effect on sedation levels compared to the tramadol group. CONCLUSION: The combined administration of naloxone and diazepam in acute-on-chronic tramadol poisoning can effectively reduce most seizure variables compared to tramadol use alone. However, none of the treatments improved sedation levels.

Effects of naloxone and diazepam on blood glucose levels in tramadol overdose using generalized estimating equation (GEE) model; (an experimental study).

BACKGROUND: Tramadol is a synthetic opioid and poisoning is increasing around the world day by day. Various treatments are applied for tramadol poisoning. Due to the unknown effects of tramadol poisoning and some of its treatments on blood glucose levels, this study was conducted to investigate the overdose of tramadol and its common treatments (naloxone, diazepam), and their combination on blood glucose levels in male rats. METHODS: This study was conducted in 45 male Wistar rats. The animals were randomly divided into five groups of 9. They received a 75 mg/kg dose of tramadol alone with naloxone, diazepam, and a combination of both of these two drugs. On the last day, animals' tail vein blood glucose levels (BGL) were measured using a glucometer at different times, including before the tramadol injection (baseline) and 1 hour, 3 hours, and 6 hours after wards. The rats were anesthetized and sacrificed 24 h after the last injection. Blood samples were then taken, and the serum obtained was used to verify the fasting glucose concentration. Data were analyzed using SPSS software at a significance level of 0.05 using a one-way analysis of variance (ANOVA) and a generalized estimating equation (GEE). RESULTS: According to the GEE model results, the diazepam-tramadol and naloxone-diazepam-tramadol groups showed blood glucose levels five units higher than the tramadol group (p < 0.05). The diazepam-tramadol group had significantly higher blood glucose levels than the naloxone-tramadol group (p < 0.05). The mean blood glucose levels before the intervention, 3 hours and 6 hours after the injection of tramadol did not differ between the groups, but the blood glucose levels 1 hour after the injection of tramadol in the group of naloxone-tramadol were significantly lower than in the control group (p < 0.05). Blood glucose levels did not differ between the groups 24 h after injection of tramadol. CONCLUSION: The results of the present study showed tramadol overdose does not affect blood glucose levels. The diazepam-tramadol combination and the diazepam-naloxone-tramadol combination caused an increase in blood glucose levels.

Association of ANGPTL3 polymorphisms with high-density lipoprotein cholesterol uptake capacity in patients with cardiovascular disease.

INTRODUCTION: Previous studies have shown the importance of angiopoietin-like 3 (ANGPTL3) as a modulator of lipid profiles. Cholesterol uptake capacity (CUC) is one means for assessing high-density lipoprotein (HDL) functionality. This study for the first time has investigated the relationship between genetic ANGPTL3 polymorphism and CUC in patients with cardiovascular disease. METHODS: Five hundred three subjects comprising 350 healthy subjects and 153 individuals who developed a cardiovascular disease (CVD) event during follow-up were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. A modified CUC method was used to determine the CUC of serum samples. Applied amplification refractory mutation system PCR was performed for ANGPTL3 variants genotyping including: rs10789117, rs1748195, and rs11207997. Sanger sequencing was applied to confirm the genotypes. RESULTS: The results showed that there was a significant relationship between the rs1748195 genotypes and HDL concentration in the CVD group (p = 0.02). Moreover, individuals with a GG genotype of the rs1748195 were associated with a lower risk of CVD (OR = 0.49, 95% CI = 0.24-0.98, p = 0.04) compared with CC genotype in the CUC ≤ 1.7 a.u subgroup. Moreover, the CT genotype of rs11207997 was associated with a lower risk of CVD (OR = 0.74, 95% CI = 0.41-1.3, p = 0.01) compared with CC genotype in CUC > 1.7 a.u subgroup. CONCLUSION: The results showed that the CT genotype of the rs11207997 variant was associated with a lower risk of incident CVD in patients with higher HDL functionality. As well, the rs1748195 gene variant may contribute to a reduced risk of CVD.

Serum HDL cholesterol uptake capacity in subjects from the MASHAD cohort study: Its value in determining the risk of cardiovascular endpoints.

BACKGROUND: The efficiency of high-density lipoprotein (HDL) to efflux cholesterol contributes to the reverse cholesterol transport (RCT) pathway as one of HDL's proposed functions and depends on the ability of HDL to uptake cholesterol. We aimed to investigate cholesterol uptake capacity (CUC) by a newly developed assay in samples from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorders) cohort study. METHOD: The study population comprised 153 individuals developed CVD diagnosed by a specialist cardiologist, over 6 years of follow-up, and 350 subjects without CVD. We used a modified CUC method to evaluate the functionality of HDL in serum samples. RESULT: The CUC assay was highly reproducible with values for inter- and intra-assay variation of 13.07 and 6.65, respectively. The mean serum CUC was significantly lower in the CVD group compared to control (p = 0.01). Although, there were no significant differences in serum HDL-C between the groups and there was no significantly association with risk of progressive CVD. Multivariate logistic regression analysis showed that there was a significantly negative association between CUC and risk of CVD after adjustment for confounding parameters (OR = 0.57, 95% CI = 0.38-0.87, p = 0.009). The CUC was also inversely and independently associated with the risk of CVD event using Cox proportional hazards models analysis (HR = 0.62; 95% CI = 0.41-0.94, p = 0.02). We determined the optimum cutoff value of 1.7 a.u for CUC in the population. Furthermore, the CUC value was important in determining the CVD risk stratification derived from data mining analysis. CONCLUSIONS: Reduced HDL functionality, as measured by CUC, appears to predict CVD in population sample from north-eastern Iran.

Prevalence of anemia and associated factors among the elderly population in South Khorasan, Birjand, 2019.

Background: Anemia is a multifactorial and common public health problem in geriatric age groups, especially in developing countries. Therefore, this study was designed to study the prevalence of anemia and associated factors among the elderly population in Birjand, Iran, in 2019. Methods: This was a cross-sectional approach to the baseline data of the Birjand longitudinal aging study (BLAS) in which 1396 people aged ≥ 60 years were screened for the presence of anemia based on the World Health Organization (WHO) criteria. For each participant, a standard questionnaire was administered. Furthermore, the height, weight, and body mass index (BMI) were calculated. Blood samples were obtained from each participant for hematological examination. Hemoglobin, hematocrit, and other indices of cell blood count were measured using an automatic cell counter. The prevalence rates were estimated using survey analysis with the weight of Birjand county older population. Univariate and multivariable logistic regression analyses were applied to detect the associated factor with anemia. Results: The mean age of the participants was 69.73±7.66 years. The crude prevalence of anemia was 11.10%, and the age-standardized prevalence based on the standard WHO population 2000-2025 was equal to 16.78% (12.81%-21.66%) (15.95% [10.41%-23.69%] in women and 17.32% (12.65%-23.25%) in men. Mild and normocytic anemia were the predominant types. The mean hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were lower in women than in men and the mean platelet count in women was higher (p<0.001). In the final multivariate logistic regression model, only age groups, BMI, fish consumption, and chronic kidney disease (CKD) were related to anemia. Conclusion: In conclusion, our findings showed the association of anemia with some risk factors and diseases. Anemia in geriatric age groups is often underdiagnosed; hence, identification of subgroups at risk for anemia and its associated risk factors in geriatric groups has a paramount importance in preventing adverse outcomes.

Tramadol and the occurrence of seizures: a systematic review and meta-analysis.

Introduction: Tramadol is a synthetic opioid which is commonly used around the world to relieve moderate to severe pain. One of the serious possible complications of its use is seizures. The present study aims to investigate and summarize the studies related to tramadol and occurrences of seizures after tramadol use and factors influencing these seizures.Methodology: Our systematic review is compliant with PRISMA guidelines. Two researchers systematically searched PubMed/Medline, Web of Sciences, and Scopus. Cohort, case-control, cross-sectional studies, and clinical trials. The risk of bias was assessed using the Newcastle-Ottawa Scale After article quality assessment, a fixed or random model, as appropriate, was used to pool the results in a meta-analysis. Heterogeneity between the studies was assessed with using I-square and Q-test. Forest plots demonstrating the point and pooled estimates were drawn.Results: A total of 51 articles with total sample size of 101 770 patients were included. The results showed that seizure event rate in the subgroups of tramadol poisoning, therapeutic dosage of tramadol, and tramadol abusers was 38% (95% CI: 27-49%), 3% (95% CI: 2-3%), 37% (95% CI: 12-62%), respectively. Tramadol dose was significantly higher in the patients with seizures than those without (mean differences: 0.82, CI 95%: 0.17-1.46). The odds for occurrence of seizures were significantly associated with male gender (pooled OR: 2.24, CI 95%: 1.80-2.77). Naloxone administration was not associated to the occurrence of seizures (pooled OR: 0.47, 95% CI: 0.15-1.49).Conclusions: Our results demonstrate that the occurrence of seizures in patients exposed to tramadol are dose-dependent and related to male gender, but not related to naloxone administration. Given that, most of the evidence derives from studies utilizing a cross-sectional design, the association of tramadol with seizures should not be considered to be definitively established.

Higher prevalence of water pipe compared to cigarette smoking among medical students in Southeast Iran.

OBJECTIVES: Smoking of water pipe (WP) and cigarettes has recently turned into a major global health burden. The present study aimed at assessing WP and cigarette smoking among Zahedan University of Medical Sciences (ZUMS) students in Iran. METHODS: A cross-sectional survey was conducted on 500 students in ZUMS (182 males, 318 females). The subjects were selected through randomized cluster sampling. Morgan's chart was applied to calculate the sample size; 96.6% of the attendees completed a questionnaire designed to address the aims of the study. RESULTS: The mean age of the subjects was 21.2 ± 2.4 years. WP and cigarette smoker rates were at 31.2% and 15.2%, respectively. The age of smoking initiation ranged between 15 and 20 years. Friends played crucial roles in triggering the smoking in both groups of WP and cigarette smokers (78% and 54%, respectively). The main reasons for WP and cigarette smoking were entertainment followed by curiosity. Furthermore, males used more cigarette (26.5 vs. 8.7%) and WP (50.6 vs. 20.4%) than females. Among father and mother smokers, respectively, 54.2% and 60% of children were also WP smokers (p = 0.001). Also, 21.9% and 60% of children smoking cigarettes had father and mother smokers, respectively (p = 0.05). CONCLUSION: Tobacco use, especially for WP seems to be at alarming rates among medical students in Iran. It is highly recommended to control the progressive prevalence of WP smoking by governmental/academic preventive measures as educational and smoking cessation activities.

Health-related Quality of Life and Associated Factors Among Thalassemia Major Patients, Southeast of Iran.

Low quality of life (QOL) is a feature that has been overlooked in thalassemia major (TM) patients. Our aim was to assess QOL in school-aged TM patients in Zabol city and surrounding rural areas in southeast of Iran. The study was performed in 2014. QOL was evaluated using Pediatric Quality of Life Inventory 4 (PedsQL4) questionnaire addressing physical, emotional, social, and educational, along with psychological health in 80 TM patients. Also, 80 age-matched and sex-matched subjects without any chronic illness served as control group. Mean age of the patients was 11.7±4.1 years old. Total QOL scores was 51.4±13.3 in the patients. In comparison, mean value of total QOL score in controls was 91.1±3.3 (P<0.0001). Poor and moderate QOL were observed in 44.7% and 48.7% of the patients, respectively. Mean functioning scores for physical, emotional, social, educational, and psychological dimensions in the patients were 56.2±119, 69.6.4±23.3, 27.1±22.1, 52.3±18.1, and 48.9±11.8, respectively. The lowest level of QOL was related to the social field (81.3% with less than average score), while the highest QOL was related to the emotional aspect (58.8% with good QOL; >75 scores). Overall, female sex, poor compliance with chelation therapy, and residency in urban areas were significantly associated with poor QOL. In conclusion, providing a psychiatric health package seems to be essential for improving QOL in TM patients, especially in social field.

Decisions Regarding Pregnancy Termination Due to ß-Thalassemia Major: a Mixed-Methods Study in Sistan and Baluchestan, Iran.

In the present study, an embedded design was applied in order to conduct a one-year cross-sectional audit of chorionic villus sampling (CVS) and foetal outcomes affected by ß-thalassemia major (ß-TM) in a prenatal diagnosis (PND) setting. In addition, we explored the decisions regarding pregnancy termination among women whose pregnancy (or child) was affected by ß-TM. In the quantitative phase, the available data in the clients' medical records were analysed, while the qualitative phase was performed using a grounded theory method. Interviews were performed with nine pregnant women who had decided against pregnancy termination despite positive CVS results, 11 mothers who had admitted their child to the thalassemia ward for blood transfusion, and 19 mothers who had received positive CVS results and had decided against pregnancy termination in the preceding year. Over one year, 18.6 % of women decided against pregnancy termination despite positive CVS results. Two main themes related to decisions against pregnancy termination emerged from the qualitative data: 1) Cognitive factors (questioning the reliability of the tests or doubts about the accuracy of the results, understanding disease recurrence, curability, perceived severity of the disease, and lack of "real-life experiences"); and 2) Sociocultural responsiveness (family opposition, responsibility before God, and self-responsiveness). All of the mentioned factors could intensify fear of abortion in couples due to possible regret, and encourage a decision against pregnancy termination.

Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms in oral squamous cell carcinoma in south-east Iran.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene encodes an essential enzyme involving in folate metabolism. Due to the role of folate in DNA integrity, polymorphisms of MTHFR are interesting targets for cancer risk studies. Our goal was to evaluate the prevalence of MTHFR C677T and A1298T single nucleotide polymorphisms in oral squamous cell carcinoma (OSCC). METHODS: The study was conducted on 57 OSCC patients diagnosed within 2004-2013 along with 62 non-OSCC subjects. DNA was extracted by standard kit protocol. Subsequently, tetra-ARMS (amplification refractory mutation system)-PCR was applied to identify the selected polymorphisms. RESULTS: Data showed that CT and TT genotypes of C677T polymorphisms significantly increased the risk of OSCC [odds ratio (OR) = 2.2, 95% CI: 1-5, P = 0.04]. Although allelic distribution was not significantly different between patients and controls, T allele of C677T polymorphism was closely associated with the risk of OSCC (OR = 2.5; 95% CI: 0.9-6.9; P = 0.07). Results indicated that C677T/A1298C: CC/AC and C677T/A1298C: CC/AA haplotypes were the most common combinations in OSCC patient and control groups, respectively. (OR = 1.5, 95% CI: 0.6-3.8, P > 0.05). CONCLUSION: Our results highlight the possible impact of C677T polymorphism in increasing the risk of OSCC development.

Molecular Characterization of ß-Thalassemia Intermedia in Southeast Iran.

Inheritance of mild mutations within the ß-globin gene and coinheritance of α-thalassemia (α-thal) are known as two important genetic modifiers in ß-thalassemia (ß-thal) intermedia (ß-TI). We aimed to evaluate the spectrum of ß- and α-thal mutations in ß-TI patients in Southeast Iran. Common ß- and α-globin gene mutations were detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and multiplex gap-PCR, respectively. There were 26 male (57.8%) and 19 female (42.2%) patients. HBB: c.92 + 5T > C [IVS-I-5 (G > C)] and HBB: c.-138C + 1G > A [IVS-II-I (G > A)] represented the prevalent alleles with respective frequencies of 60.0 and 10.0%. Other ß-globin mutations included HBB: c.-138C > T [-88 (C > T)], HBB: c.27_28insG [frameshift codons (FSC) 8/9 (+G)], HBB: c.46delT [codon 15 (-T)], HBB: c.93-22_95del (IVS-I, 25 del), and the 619 bp deletion (NG_000007.3: g.71609_72227del619). The predominant genotypic combinations were ß(0)/ß(0) (68.9%), ß(0)/ß(+ )(8.9%) and ß(+)/ß(+ )(2.2%). Coinheritance of α-thal was observed in 33.0% of the patients, with the -α(3.7) (rightward) (NG_000006.1: g.34164_37967del3804) as the most common deletion (86.0%). One patient was diagnosed with the -α(4.2) (leftward) (AF221717) and one with the - -(MED) (g.24664_41064del16401) deletions, while no patients carried the -(α)(20.5) (g.15164_37864del22701), α(-5 nt) (HBA2: c.95 + 2_95_6delTGAGG) or codon 19 (-G) (HBA2: c.56delG) mutations. The alleviating molecular mechanism was not explainable by ß(+ )or concurrent α-thal in more than half of our ß-TI patients. This encourages conducting more studies to identify other contributing factors, especially Hb F-inducing genetic modifiers.

Intracranial hemorrhage pattern in the patients with factor XIII deficiency.

Intracranial hemorrhage (ICH) is one of the most severe and life-threatening manifestations occurring in the patients with factor XIII (F XIII) deficiency. The aim of this study was to describe the ICH pattern in the patients suffering from F XIII deficiency. In this case series, we investigated 38 patients with severe F XIII deficiency in south of Iran from January to May 2012. ICH pattern, neurologic complications, efficacy of treatment, and incidence of recurrence were reported. The site of ICH was intraparenchymal in 35 patients (92.1 %), subdural in 2 patients (5.2 %), and epidural hemorrhage in 1 patient (2.6 %). Besides, neurologic complications occurred in 21 patients (55.2 %), including locomotor disability in 8, psychological impairment in 7, mental disorders in 5, speech impairment in 4, and visual impairment in 2. Prophylaxis was started with a dose of 10 IU/kg Fibrogammin every 4-6 weeks for all the patients, except for one. All the patients on prophylaxis showed good response without any episodes of recurrence, except for one. The most frequent site of ICH in our patients was intraparenchymal. It seems that long-term prophylactic treatment with a dose of 10 IU/kg Fibrogammin could be effective in the prevention of CNS bleeding in the patients with F XIII deficiency. Moreover, all the patients with severe F XIII deficiency even without severe bleeding symptoms are recommended to undergo prophylactic treatment.

A local equation for differential diagnosis of ß-thalassemia trait and iron deficiency anemia by logistic regression analysis in Southeast Iran.

The most common differential diagnosis of ß-thalassemia (ß-thal) trait is iron deficiency anemia. Several red blood cell equations were introduced during different studies for differential diagnosis between ß-thal trait and iron deficiency anemia. Due to genetic variations in different regions, these equations cannot be useful in all population. The aim of this study was to determine a native equation with high accuracy for differential diagnosis of ß-thal trait and iron deficiency anemia for the Sistan and Baluchestan population by logistic regression analysis. We selected 77 iron deficiency anemia and 100 ß-thal trait cases. We used binary logistic regression analysis and determined best equations for probability prediction of ß-thal trait against iron deficiency anemia in our population. We compared diagnostic values and receiver operative characteristic (ROC) curve related to this equation and another 10 published equations in discriminating ß-thal trait and iron deficiency anemia. The binary logistic regression analysis determined the best equation for best probability prediction of ß-thal trait against iron deficiency anemia with area under curve (AUC) 0.998. Based on ROC curves and AUC, Green & King, England & Frazer, and then Sirdah indices, respectively, had the most accuracy after our equation. We suggest that to get the best equation and cut-off in each region, one needs to evaluate specific information of each region, specifically in areas where populations are homogeneous, to provide a specific formula for differentiating between ß-thal trait and iron deficiency anemia.

Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

BACKGROUND: Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). OBJECTIVE: In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. RESULTS: Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. CONCLUSION: We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

Prevalence and molecular identification of the mediterranean variant among G6PD-deficient Sistani and Balouch males in Southeastern Iran.

To determine the prevalence of G6PD deficiency and a Mediterranean mutation among males in southeastern Iran, we studied 1,097 Sistani and Balouch schoolboys. A questionnaire was used to collect demographic data and a history of malaria infection; blood samples were evaluated for G6PD deficiency and the G6PD Mediterranean mutation. Of the 1,097 boys screened, 175 were G6PD deficient (5.8 % of the Sistani boys and 19.3 % of the Balouch boys). The malaria survey indicated that among Balouch subjects, malaria infection was about 14 times that of Sistani subjects. Molecular characterization of G6PD-deficient samples revealed a general frequency of 85.1 % for the Mediterranean variant among all subjects (75 % among Sistani and 86.2 % among Balouch cases). The high prevalence of G6PD deficiency among Balouch populations confirms the hypothesis that the distribution of G6PD deficiency is concordant with the geographic distribution of malaria.