Genetic association of IL2RA, IL17RA, IL23R, and IL31RA single nucleotide polymorphisms with alopecia areata.

The signalling of cytokine receptors plays a crucial role in regulating tolerance and immunity. Impaired immunological processes result in autoimmune inflammation that target the hair follicles, causing many hair disorders, mainly alopecia areata (AA). Therefore, polymorphisms in cytokine receptor genes are suggested to have a significant impact on the pathogenesis of AA, a disease with a multifactorial basis and uncertain etiology. In the present study, 152 AA patients of the Jordanian population were investigated for their genetic susceptibility to develop AA compared to 150 control subjects. Genomic DNA extraction and genotyping had conducted for IL17RA (rs879575, rs2229151, and rs4819554), IL2RA (rs3118470), IL23R (rs10889677), and IL31RA (rs161704) using the Sequenom MassARRAY® system. The allele frequency of IL17RA rs879575 is significantly higher in patients, while no statistical differences were found for IL2RA, IL23R, and IL31RA SNPs. Also, the recessive model of IL31RA rs161704 showing that AA genotype is significantly associated with AA development. To date, there is no published data regarding the association between AA and the selected genetic variants in our population. However, this study's findings assert that SNPs of IL17RA and IL31RA are linked to AA susceptibility in Jordanian patients.

Genetic Association between Interleukin Genes and Alopecia Areata in Jordanian Patients.

Objectives: Alopecia areata (AA) is a multifactorial autoimmune disease with a strong genetic predisposition. A variety of genes involved in immunity and inflammatory responses, such as cytokines, are suspected to increase the risk of developing AA. In which, different interleukin (IL) genes that associated with several autoimmune diseases and AA in varied populations. The objective of this study was to investigate the possible genetic association of AA with ten variants of single nucleotide polymorphism (SNP) in IL12B,IL13,IL16,IL17A, and IL18 genes among Jordanian patients. Methods: In this case-control study, peripheral blood samples of 152 Jordanian AA patients and 150 controls (total of 302 subjects) were collected, genomic DNA extracted and genotyped, based on which their allele and genotype frequencies were assessed. Results: In the rs11073001 SNP located in the exon region of the IL16 gene, the A allele was distributed more frequently in AA patients (p =0.01). A difference was found between the patients and the controls for the rs17875491 SNP in the promoter region of the IL16 gene (p =0.04). The mean age of onset was 27.3±12.6 with male predominance. Most patients (68.4%) were asymptomatic but some reported experiencing associated sensations before the hair loss episodes. The patchy patterns of alopecia were the most common (90.3%). Nail changes were found in 7.3% of the patients. Conclusions: The findings support the hypothesis of the involvement of IL16 gene in the etiology of AA. Moreover, it emphasizes the variations in the genetic component of AA, as well as the clinical phenotypes among different ethnic groups.

Genetic predisposition of alopecia areata in jordanians: A case-control study.

Alopecia areata (AA) is a common non-scarring hair loss disease of defined patterns with varied patches size and body sites. The etiology of AA has a complex basis of autoimmunity, environment, and genetic variations. The latter factor is found to play a crucial role in AA risk. Thus, this study aimed to investigate the potential impact of specific immune-related gene polymorphisms among a cohort of Jordanian patients, which was previously reported in other populations. Blood samples of AA patients and control subjects were collected for genomic DNA (gDNA) extraction. Targeted single nucleotide polymorphisms (SNPs) of MASP2, TLR1, CTLA4, and C11orf30 were genotyped in duplicate using the Sequenom MassARRAY® system (iPLEX GOLD). Genotype and allele analysis reveals statistical differences in TLR1 rs4833095 (allele C, P = 0.044), MASP2 rs2273346 (genotype AA, P = 0.0026), and C11orf30 rs2155219 (genotype GG, P = 0.0069) distribution. These findings present the significant contribution of genetic variations in AA susceptibility in the Jordanian population, which is infrequently studied.

Genetic Association of Epilepsy and Anti-Epileptic Drugs Treatment in Jordanian Patients.

PURPOSE: The aim of this study was to investigate the possible effects of single-nucleotide polymorphisms (SNPs) within SLC1A1, SLC6A1, FAM131B, GPLD1, F2, GABRG2, GABRA1, and CACNG5 genes on response to anti-epileptic drugs (AEDs) and the genetic predisposition of epilepsy in Jordanian patients. PATIENTS AND METHODS: A total of 299 healthy individuals and 296 pediatric patients from the Jordanian population were recruited. Blood samples are collected, and genotyping was performed using a custom platform array analysis. RESULTS: The SLC1A1 rs10815018 and FAM131B rs4236482 polymorphisms found to be associated with epilepsy susceptibility. Moreover, SLC1A1 rs10815018 and GPLD1 rs1126617 polymorphisms were associated with generalized epilepsy (GE), while FAM131B rs4236482 is associated with the focal phenotype. Regarding the therapeutic response, the genetic polymorphisms of FAM131B rs4236482, GABRA1 rs2279020, and CACNG5 rs740805 are conferred poor response (resistance) to AEDs. There was no linkage of GLPD1 haplotypes to epilepsy, its subtypes, and treatment responsiveness. CONCLUSION: Our findings suggested that SLC1A1, FAM131B, and GPLD1 polymorphisms increasing the risk of generating epilepsy, while FAM131B, GABRA1, and CACNG5 variants may play a role in predicting drug response in patients with epilepsy (PWE).

Application of Gas Chromatography-Mass Spectrometry for the Identification and Quantitation of Three Common Synthetic Cannabinoids in Seized Materials from the Jordanian Market.

Synthetic cannabinoids (SCs) were developed to mimic the effects of Δ9-tetrahydrocannabinol on humans. SCs were distributed in the form of herbal blends, with smoking being the main method of consumption. These synthetic compounds have a wide range of physical, behavioral, and harmful effects on the body. However, this study aimed to identify and quantify three common SCs including AB-FUBINACA, AB-CHMINACA, and XLR-11 in the seized materials from the Jordanian market by gas chromatography coupled with mass spectrometry (GC-MS). A liquid-liquid extraction sample preparation technique was applied to 100 different seized samples obtained from the Anti-Narcotics Department of Public Security in a period between 2017 and 2018. Profiling of the seized samples revealed different distributions of the targeted SCs in the obtained samples. Upon quantitation, concentrations of these SCs varied greatly within and among the samples. The use of GC-MS analysis provided a powerful technique in the detection and identification of SCs. This study revealed the current and trends of SC use in the Jordanian illicit substance market, which was previously unclear. Future studies are required to explore new SCs and their influence in different biological samples.

Candidate Gene Analysis Of Alopecia Areata In Jordanian Population Of Arab Descent: A Case-Control Study.

BACKGROUND: Alopecia areata (AA) is a non-cicatricial patchy hair loss on the scalp, face or other parts of the body. AA was found to be responsive to immunosuppressive therapies, a finding that supports an autoimmune basis for the disease. Several genetic studies have shown the significance of immunological factors as key genetic components in AA. OBJECTIVE: In this study, we aimed to investigate the genetic association of 7 single-nucleotide polymorphisms (SNPs) within five candidate genes including TAP1, CXCL1, CXCL2, HSPA1B, and TNFα with AA susceptibility in the Jordanian Arab population. METHODS: A case-control genetic association study conducted in 152 patients and 150 healthy individuals was performed using the sequenom MassARRAY system (iPLEX GOLD) to genotype the selected SNPs. RESULTS: rs1800629 SNP of the TNFα gene was significantly associated with AA in the heterozygous and rare homozygous genotypes (P=0.022 and P=0.0079, respectively) with no linkage of the TAP1, CXCL1, CXCL2 and HSPA1B variants. CONCLUSION: This is the first study of its kind among the Jordanian population providing evidence of genetic association of the TNFα with AA susceptibility. Further genetic studies on Arab descent including other variants are required to clarify and strengthen the association of these genes with susceptibility to develop AA.

Genetic polymorphisms of CYP3A5, CHRM2, and ZNF498 and their association with epilepsy susceptibility: a pharmacogenetic and case-control study.

BACKGROUND: A total of 50 million persons were diagnosed worldwide with epilepsy. One-third of them are experiencing debilitating seizures despite optimum anti-epileptic drugs (AEDs) treatment. Several studies have suggested that CYP3A5, CHRM2, and ZNF498 influence the pharmacokinetics of AEDs. Therefore, the severity of the disease as well as the degree of response to the AEDs could be affected by the genetic polymorphisms within these genes. OBJECTIVES: In this study, we assessed the effect of certain single nucleotide polymorphisms (SNPs) within CYP3A5, CHRM2, and ZNF498 genes on the susceptibility to develop epilepsy and the responsiveness to AEDs treatment. METHODS: A case-control and pharmacogenetic study was conducted on samples of 299 healthy individuals in addition to 296 epileptic patients. Genotypic, allelic, and clinical data association were performed for the selected polymorphisms within the (rs324649, rs420817, rs15524, and rs1859690) in the Jordanian population. RESULTS: The analysis revealed no significant association of the investigated SNPs with epilepsy in general, partial and generalized epilepsy as well as drug responsiveness. CYP3A5 and ZNF498 were associated with family history (P=0.003 and P=0.002, respectively) and the classification of epilepsy for the ZNF498 variant (P=0.009). On the other hand, CHRM2 was not linked to either disease severity or treatment responsiveness. CONCLUSION: Our results failed to confirm the association of CYP3A5, ZNF498, and CHRM2 variants with either disease development or treatment response. Clinical pharmacogenetic studies may contribute to treatment personalization, appropriate drug dose selection, minimizing drug adverse reactions, increasing drug efficacy, and reducing the costive burdens.

Effects of GRM4, SCN2A and SCN3B polymorphisms on antiepileptic drugs responsiveness and epilepsy susceptibility.

BACKGROUND: Pharmacotherapy of epilepsy including antiepileptic drugs (AEDs) is one of the main treatment approaches. As a biological target, sodium channels (Nav channels) and glutamate receptor genes are playing a major role in the etiology and treatment of epilepsy. OBJECTIVE: This study aims to investigate the genetic associations of certain genetic polymorphisms with increased risk of epilepsy susceptibility and variability in response to AEDs treatment in a Jordanian Arab population. METHOD: A pharmacogenetics and case-control study on 296 unrelated epileptic Jordanian patients recruited from the pediatric neurology clinic at the Queen Rania Al-Abdullah Hospital (QRAH) in Amman, Jordan and 299 healthy individuals was conducted. Children up to 15 years old which receiving AEDs for at least three months were scanned for genetic association of 7 single nucleotide polymorphisms (SNPs) within three candidate genes (SCN2A, SCN3B and GRM4) with epilepsy susceptibility. RESULTS: SCN2A rs2304016 (P = 0.04) and GRM4 rs2499697 (P = 0.031) were statistically significant with generalized epilepsy. Haplotype of CAACG GRM4 was genetically associated with epilepsy and partial epilepsy (P = 0.036; P = 0.024, respectively). This study also found that TGTAA genetic haplotype formed within GRM4 gene was associated with generalized epilepsy susceptibility (P = 0.006). While, no significant linkage of SCN3B rs3851100 to either disease susceptibility or drug responsiveness was found. CONCLUSION: This study identified no significant associations of allelic or genotypic SNPs with the susceptibility of epilepsy and medication response with an exception of rs2304016 and rs2499697 SNPs that were associated with the generalized type of epilepsy among Jordanian population. Further studies are required in different populations to confirm our results and identify genetic factors that involved in susceptibility and treatment response.

Effects of MTHFR and ABCC2 gene polymorphisms on antiepileptic drug responsiveness in Jordanian epileptic patients.

BACKGROUND: Epilepsy is one of the most common neurological diseases with unclear etiology where its genetic background and treatment regime still need further exploration. OBJECTIVES: This study designed to evaluate the pharmacogenomics of MTHFR and ABCC2 genes, and their association with epilepsy susceptibility among Jordanian population. METHODS: A case-control study was conducted on Jordanian cohort of 296 epileptic patients and 299 healthy individuals. Custom platform array was used to genotype the genetic polymorphisms within MTHFR (rs1801133) and ABCC2 (rs717620, rs3740066, rs2273697) genes. RESULTS: This study revealed a significant genetic association of MTHFR rs1801133 polymorphism with susceptibility to generalized in general and generalized tonic-clonic epilepsy (GTCE)(p=0.018 and 0.01, respectively). Regarding ABCC2 gene, rs717620 was of linkage with generalized and GTCE subtypes (p=0.045 and 0.048, respectively), while rs717620 was associated with poor responder patients (p=0.036) with no linkage of the ABCC2 haplotypes. CONCLUSIONS: MTHFR and ABCC2 polymorphisms showed an association with either epilepsy types in general or subtypes and treatment response among Jordanian population. This study also suggested that these gene polymorphisms have an important role in epilepsy development and drug effectiveness and could be of a great impact in the era of epilepsy diagnosis and treatment.

Gas chromatographic-mass spectrometric analysis of sunscreens and their effects on mice liver and kidney enzyme function.

BACKGROUND: Sunscreens are one of the most widely used products among cosmetics and personal care products. Recent studies have shown that some of sunscreen formulations may contain toxic, carcinogenic, or even nonallowed chemicals that may affect skin, cells, and hormones. MATERIALS AND METHODS: This study aimed to develop and validate a method that allows the determination of sunscreen ingredients by gas chromatography-mass spectrometry (GC-MS). Analysis of original sunscreen products (n=5) from a licensed pharmacy and counterfeit sunscreen products (n=5) from local markets in Jordan was performed using GC-MS. pH stability of the sunscreen samples were also monitored under different storage temperatures. Topical application of sunscreens on mice skin was conducted to study their effects on liver and kidney enzymes' function. RESULTS: In terms of pH stability, there is a significant change in pH at different degrees of temperature between the products. Diethyl phthalate (DEP) was detected in two counterfeit products and was not mentioned on the ingredients' label. DEP was reported for its percutaneous absorption and systemic uptake in the literature. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly increased with a P<0.005 in some groups treated with original sunscreens under sun radiation. Creatinine showed a significant decrease in some groups treated with original and counterfeit sunscreens, while blood urea nitrogen (BUN) showed no differences. CONCLUSION: This study presents a method that allows the scanning and profiling of sunscreen ingredients as well as investigates their stability, permeation, and toxicity. Profiling of sunscreen product, changing in pH stability, and analyzing kidney and liver enzymes' level would be of a great impact on products' safety and consumers' health.