ABCG2, SCN1A and CYP3A5 genes polymorphism and drug-resistant epilepsy in children: A case-control study.

PURPOSE: Drug Resistant -Epilepsy is still a major challenge in pharmacotherapy of epilepsy. Pharmacogenetic pathways are one of the most important elements that can help clinicians determine medication response and provide more efficient drug therapy, especially in cases of drug resistance. Genetic alterations in drug target and transporter proteins, in part, could explain the development of drug-resistant epilepsy. We sought to assess the association of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) candidate polymorphisms with drug-resistant epilepsy among Iranian children with epilepsy. METHODS: In a hospital-based case-control study, 93 participants, including 45 men and 48 women aged 1.5 to 14 years old were recruited. Genotyping of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) polymorphisms using the high-resolution melting (HRM) method were measured in 46 children with drug-resistant epilepsy and 47 healthy control subjects. The binary logistic regression model was used to estimate the odds ratio (OR) for each polymorphism per effect allele increase. RESULTS: The mean (standard deviation [SD]) age of the drug-resistant patients was 10.7 (9.0) years versus 7.3 (3.6) in the control group. In the case group, most of the patients with epilepsy were diagnosed with generalized seizure (about 87%) and negative epileptic history status (63%). Furthermore, idiopathic epilepsy was dominant in the case group (69%). There was a clinically meaningful increase in the chance of drug-resistant epilepsy in participants with candidate polymorphism in ABCG2 gene (per allele T increase, adjusted odds ratio [OR] 2.41, confidence interval [CI] 0.99 to 5.87, P=0.05). No significant association was found between CYP3A5 (per allele C increase, OR 0.92, CI 0.33 to 2.60, P= 0.88) and SCN1A (per allele *1 increase, OR 0.65, 95% CI 0.34 to 1.23, P= 0.19) with drug-resistant epilepsy. CONCLUSION: We found evidence for the relationship between the ABCG2 gene polymorphism and a higher chance of drug-resistant epilepsy in children. This finding may have important implications for understanding the role of ABCG2 gene polymorphism in children with drug-resistant epilepsy.

The effect of acidic beverage versus mineral water on the change in serum phenobarbital concentrations: a randomized clinical trial on children with seizure.

OBJECTIVE: To assess the effect of an acidic beverage (Orange juice) on the change in serum Phenobarbital concentrations in children with seizure who take Phenobarbital as the main treatment. METHODS: We did a parallel design and placebo controlled randomized clinical trial. Patients attending Heshmatiyeh Hospital (Iran) were recruited from October 2016 to December 2017. Forty patients randomly assigned to either experimental group or control group. Firstly, 5 mL blood sample was taken from both groups to measure serum Phenobarbital concentration before experiment. Then, one oral dose of Phenobarbital (2.5 mg/kg) with 100 mL of corporate Orange juice (pH = 3.5) (experiment group) or 100 mL of mineral water (neutral pH) (control group) was given to each group, respectively. After 2 h of administration, another blood sample was taken. The high-performance liquid chromatographic system was used for measurement of serum Phenobarbital concentration. RESULTS: There was significant increase in serum Phenobarbital concentrations after taking Phenobarbital in experiment group in comparison to control group. Statistical analysis revealed a significant increase in change of serum Phenobarbital concentrations in experiment group versus control group. CONCLUSION: The results of the current trial indicate that the level of serum Phenobarbital in the experiment group was higher than that of control group.

Human T-lymphotropic virus type 1 prevalence in northeastern Iran, Sabzevar: an epidemiologic-based study and phylogenetic analysis.

Human T-lymphotropic virus type 1 (HTLV-I) is an important global health problem in the world mainly in the endemic areas of HTLV-I infection. It was previously reported that Mashhad, in northeastern Iran, is a new endemic region of HTLV-I. The aim of this study was to examine the prevalence and phylogenetic analysis of HTLV-I in Sabzevar, located in the southeast of Mashhad. In this cross-sectional study 1445 individuals were selected by multistage cluster sampling. Serum samples were screened for anti-HTLV-I antibody using enzyme-linked immunosorbent assay (ELISA); all of the ELISA-positive samples were confirmed by polymerase chain reaction (PCR). Long terminal repeat (LTR) sequencing was carried out to determine the type of HTLV-I in Sabzevar. In the primary screening by ELISA, 26/1445 (1.8%) of those sampled were reactive for HTLV-I antibody. Twenty-four out of 26 samples were confirmed HTLV-I infection by PCR (24/1445). The overall prevalence of HTLV-I infection in Sabzevar is 1.66%. The prevalence of the virus infection in men and women was 2.42% (11/455) and 1.31% (13/989), respectively. Seroprevalence was associated with age, increasing significantly among those older than 30 years (p=0.015), and a history of surgery (p=0.002), imprisonment (p=0.018), and hospitalization (p=0.005). Three out of 24 positive HTLV-I samples were selected for sequencing and phylogenetic analysis of LTR. The results showed that HTLV-I in Sabzevar belonged to the cosmopolitan subtype. The present study showed Sabzevar is a new endemic area for HTLV-I infection. Our study emphasizes that systemic HTLV-I screening of blood donors in Sabzevar and other cities in Khorasan province is important and should be taken into account.