Single-nucleotide polymorphisms associated with pemphigus vulgaris: Potent markers for better treatment and personalized medicine.

Pemphigus vulgaris (PV) is a rare autoimmune blistering disorder, which could affect both skin and mucosal surfaces. There is increasing evidence that genetics plays a critical role in PV development, severity and prognosis. Single-nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people and have been widely evaluated in most diseases. However, there are few studies regarding the roles of SNPs in the PV. Here, we reviewed both pathogenic and protective roles of the SNPs in non-HLA genes regarding the PV. Among the large number of studied SNPs, it was found that several SNPs in different genes might control the susceptibility of PV, including TNFA (rs361525, rs1800629, rs1800629), IL10 (rs1800871, rs1800896, rs1800871, and rs1800872), IL6 (rs1800795), CTLA4 (rs231775), ICOS (rs10932029), CD86 (rs1129055), DSG3 (rs8085532, rs3911655, rs3848485, rs3794925, rs1466379), ST18 (rs2304365, rs17315309) and TAP2 (rs7454108), probably in a population-specific manner. Moreover, SNPs in glucocorticoid receptor, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, including rs11745958, rs17209237, rs33388, rs7701443 as well as rs116855232 at NUDT15, seem to be associated with therapeutic outcomes in PV patients. Additionally, variations in the other genes involved in the drugs' metabolisms, pharmacokinetics and pharmacodynamics such as rs396991 in FCGR3A gene could be used for the prediction of clinical response to drugs and side effects. Taken together, SNPs seem to be valuable tools for better management of PV patients. Further studies need to be conducted to evaluate SNPs in genes that control immune responses and apoptosis.

The Effect of Filial Therapy on Depressive Symptoms of Children with Cancer and Their Mother's Depression, Anxiety, and Stress: A Randomized Controlled Trial.

BACKGROUND: Childhood cancer is an overwhelming life event that can completely change the lives of the sufferers and their parents. Todays, advances of medical science have shifted the fetal nature of childhood cancer to chronic one exposing children and their family to behavioral and psychosocial problems. The aim of this study was to investigate the effect of filial therapy on children's depressive symptoms and their mother's stress, anxiety, and depression. MATERIALS AND METHODS: In this randomized controlled trial, 32 mothers with their children who suffered from cancer were recruited (16 in each group). During a 10-week training sessions, filial therapy group underwent child-parent relation therapy (CPRT). Training sessions were held once a week. Control group received no training and only individual counseling sessions were held for them we needed. Both groups were assessed before and after the intervention using depression, anxiety, and stress questionnaire-21 (DASS-21), children depression inventory (CDI), and Wong-Baker faces pain rating scale (WBFPRS). Sample randomization and data analysis were conducted by using SPSS (version 20) and running independent t-test and chi-square test. P value< 0.05 was set as the significant level. RESULTS: Mothers in the filial therapy group experienced significant decrease in their level of depression, anxiety, and stress in the posttest (p < 0.001). In contrast to filial therapy group, mothers in the control group did not show an improvement in their level of depression, anxiety, and stress. Moreover, the results of the current investigative showed that depression of children in the filial therapy group significantly reduced at post-test (p < 0.001). On the other hand, the mean of children's depression in the control group remained steady. CONCLUSION: The findings of the present study revealed that using filial therapy could reduce the depression of children with cancer and their parent's depression, anxiety, and stress. Accordingly, we suggest filial therapy programs as a routine for addressing psychosocial problems of children with cancer and their families.

Structural analysis of missense mutations in galactokinase 1 (GALK1) leading to galactosemia type-2.

Galactosemia type 2 is an autosomal recessive disorder characterized by the deficiency of galactokinase (GALK) enzyme due to missense mutations in GALK1 gene, which is associated with various manifestations such as hyper galactosemia and formation of cataracts. GALK enzyme catalyzes the adenosine triphosphate (ATP)-dependent phosphorylation of α-d-galactose to galactose-1-phosphate. We searched 4 different literature databases (Google Scholar, PubMed, PubMed Central, and Science Direct) and 3 gene-variant databases (Online Mendelian Inheritance in Man, Human Gene Mutation Database, and UniProt) to collect all the reported missense mutations associated with GALK deficiency. Our search strategy yielded 32 missense mutations. We used several computational tools (pathogenicity and stability, biophysical characterization, and physiochemical analyses) to prioritize the most significant mutations for further analyses. On the basis of the pathogenicity and stability predictions, 3 mutations (P28T, A198V, and L139P) were chosen to be tested further for physicochemical characterization, molecular docking, and simulation analyses. Molecular docking analysis revealed a decrease in interaction between the protein and ATP in all the 3 mutations, and molecular dynamic simulations of 50 ns showed a loss of stability and compactness in the mutant proteins. As the next step, comparative physicochemical changes of the native and the mutant proteins were carried out using essential dynamics. Overall, P28T and A198V were predicted to alter the structure and function of GALK protein when compared to the mutant L139P. This study demonstrates the power of computational analysis in variant classification and interpretation and provides a platform for developing targeted therapeutics.

TNF-α -308G/A gene polymorphism in bullous pemphigoid and alopecia areata.

BACKGROUND: TNF-α -308G/A polymorphism has been investigated in few studies for an association with susceptibility to bullous pemphigoid (BP) and alopecia areata (AA). Yet, these findings had so far not been independently replicated, and no data on a possible association of TNFα -308G/A polymorphism with these diseases in Iranian population were available. OBJECTIVES: In the present study, a possible effect of TNF-α -308G/A variation on susceptibility to BP or AA disease was evaluated. METHODS: Genomic DNA was extracted from the blood of the patients with BP and AA as well as control subjects which genotyped for the TNF-α -308 G/A polymorphism. TNF-α gene expression levels were analyzed by real-time RT-PCR. RESULTS: No association was observed between the TNF-α -308 G/A variation and susceptibility to BP or AA diseases in our Iranian cohort. In contrast to AA patients, expression of TNF-α gene was significantly higher in BP patients compared to control group. TNF-α gene was found to be similarly expressed in mutant and wild-type genotypes. CONCLUSIONS: TNF-α -308G/A polymorphism is not associated with the risk to develop of BP and AA in our Iranian cohort. Furthermore, this polymorphism is contributed to altering the levels of gene expression in BP disease.