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Background: Carbamazepine (CBZ) is widely used as an anti-epileptic drug. Vitamin B12 has been shown to protect against DNA damage caused by several mutagenic agents. Objective: This study aimed to investigate the effect of vitamin B12 on CBZ-induced genotoxicity in cultured human lymphocytes. Methods: Sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) genotoxic assays were utilized to achieve the study objective. Results: The results showed significantly higher frequencies of CAs and SCEs in the CBZ-treated cultures (12 μg/mL) compared to the control group (P Conclusion: CBZ is genotoxic to lymphocyte cells, and this genotoxicity can be reduced by vitamin B12.

This preliminary investigation aimed to assess the DNA found in human bones and teeth recovered from the archaeological site of Tell Damiyah. The primary objective was to gather data that could contribute to the ongoing archaeological research focused on understanding the migration patterns of ancient societies in the Central Jordan Valley of southern Levant and their interactions with the surrounding regions. The bone and teeth samples, obtained from the Byzantine and Ottoman contexts at Tell Damiyah, were subjected to DNA extraction and analysis. The results revealed that only two teeth samples from the Byzantine period contained viable DNA suitable for extraction. This was due to the suboptimal preservation of DNA in the remaining samples. Consequently, the DNA data obtained from this study were included in the human DNA database of cultural heritage sites in Jordan, enabling comparison and interpretation with future DNA data obtained from comparable samples. As a result, it is recommended to conduct further DNA investigations on bone and teeth samples, particularly those obtained from recently excavated contexts at Tell Damiyah or other related and comparable sites.

In early embryogenesis, aortic anomalies occur as a consequence of disorders in the development of the primitive aortic arches system. Aberrant right subclavian artery, also known as arteria lusoria, is one of the important congenital anomalies of the aortic arch, in which the right subclavian artery arises from the arch of aorta instead of the brachiocephalic trunk. During routine dissection of a female cadaver, we observed retro-oesophageal aberrant right subclavian artery arising as the fourth branch from the aortic arch. In this case, the brachiocephalic trunk was absent. Early detection of aortic arch anomalies through diagnostic interventions is helpful to avoid complications during surgical procedures.

CYP2C8 is a member of Cytochrome P450 enzymes system. It plays an important role in metabolizing a wide range of exogenous and endogenous compounds. CYP2C8 is involved in the metabolism of more than 100 drugs, typical substrates include: anticancer agents, antidiabetic agents, antimalarial agents, lipid lowering drugs and many others that constitute 20% of clinically prescribed drugs. Genetic variations of CYP2C8 have been reported with different frequencies in different populations. These genetic polymorphisms can lead to differences in the efficacy and safety of different types of medications metabolized by CYP2C8. The aim of this study was to investigate the allele frequencies of CYP2C8*3 (rs10509681 and rs11572080) and CYP2C8*4 (rs1058930) polymorphisms in three populations living in Jordan; Circassians and Chechens and Jordanian-Arabs and compare those frequencies with other populations. A total of 200 healthy Jordanians, 93 Circassians and 88 Chechens were included in this study. Genotyping of CYP2C8*3 and CYP2C8*4 polymorphisms was done by using polymerase chain reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP). Using the Chi-square test, we found that the prevalence of CYP2C8*3 and *4 among the three populations were significantly different. Moreover, the mutant allele CYP2C8*3 (416A) was only detected in the Jordanian-Arab population with an allele frequency of 0.082, while the mutant allele CYP2C8*4 (792G) was detected with frequencies of 0.065, 0.122, 0.017 in Jordanian-Arabs, Circassians and Chechens, respectively. As our results show, CYP2C8*3 was undetectable in our Circassians and Chechens samples, on the other hand, Circassians had the highest allele frequency of CYP2C8*4 compared to Chechens and Jordanian-Arabs. These genetic variations of the gene encoding the CYP2C8 drug metabolizing enzymes can lead to clinical differences in drug metabolism and ultimately variations in drug effectiveness and toxicities. This study provides evidence for the importance of personalized medicine in these populations and can be the foundation for future clinical studies.

Background: Helicobacter pylori (H. pylori) infection is the most common cause of peptic ulcer disease and it can be associated with many complications, including malignancies. In clinical practice, some clinicians may use Clavulanic Acid (CA) in combination with amoxicillin or other beta-lactams as an addition to the standard treatment regimens. This practice may be done by habitual mistake, non-evidence based hypothetical assumptions, or by prescribing it as an alternative treatment. This review aims to expose the effect of CA against H. pylori infection and to review the possible mechanisms that may contribute to that effect. Methods: A PubMed and Google Scholar literature search was obtained on both pre-clinical and clinical studies related to CA and H.pylori infection. Results: Available clinical studies showed improvement in the eradication of H. pylori by about 10- 20% when CA was added to the treatment regimens. This effect for CA could be related to several mechanisms including inhibition of H. pylori growth by binding to Penicillin-Binding Proteins (PBPs), the transformation of H. pylori from the active filamentous form into coccoidal form, induction of the release of dopamine, modulation of immunological response towards H. pylori infection and its relationship with other microbiota. Randomized-controlled studies on patients with resistance to H. pylori are needed. Moreover, in vitro studies to evaluate the mechanisms by which CA may influence H. pylori are warranted. Conclusion: The presented literature suggests potential avenues for the use of CA in the management of peptic ulcer disease and H.pylori infection.

Cardiovascular diseases are among the leading causes of death worldwide. Many of those diseases require treatment with warfarin, an anticoagulant that has a large high inter and intra-variability in the required doses. The aim of this study is to find if there are any associations between rs2108622 of CYP4F2, rs7412 and rs405509 of ApoE, and rs1801272 of CYP2A6, and CVD and warfarin dose variability. The selected genes and their polymorphisms are involved in many GWAS associated with cardiovascular disease and variability in warfarin treatment. The study sample consisted of 212 Jordanian Cardiovascular patients and 213 healthy controls. DNA was extracted and the Mass ARRAY™ system was used to genotype four selected SNPs within three genes (CYP4F2, ApoE, and CYP2A6). Only one out of the four selected SNPs (ApoE rs7412 SNP) was found to be associated with the risk of cardiovascular disease. Also, this SNP showed significant differences in warfarin initial doses. CYP2A6 rs1801272 SNP was found to be associated with warfarin sensitivity during the initiation phase of therapy and with warfarin responsiveness and INR measurement during the stabilization phase of therapy. This study improves the current understanding of the high inter and intra-variabilities in response to warfarin, including the variety of dosing requirements and the susceptibility to cardiovascular disease in the Jordanian Arab population. Further study on a larger sample and in different ethnic groups could help in improving our understanding of warfarin's pharmacogenetics and its application in personalized medicine.

Infection with the human papillomaviruses (HPV) often involves the epigenetic modification of the host genome. Despite its prevalence among the population, host genome methylation in HPV-induced warts is not clearly understood. In this study, genome-wide methylation profiling was carried out on paired healthy skin and wart samples in order to investigate the effects that benign HPV infection has on gene methylation status. To overcome this gap in knowledge, paired wart (n = 12) and normal skin (n = 12) samples were obtained from Arab males in order to perform DNA extraction and subsequent genome-wide methylation profiling on the Infinium Methylation EPIC Bead Chip microarray. Analysis of differential methylation revealed a clear pattern of discrimination between the wart and normal skin samples. In warts, the most differentially methylated (DM) genes included long non-coding RNAs (AC005884, AL049646.2, AC126121.2, AP001790.1, and AC107959.3), microRNAs (MIR374B, MIR596, MIR1255B1, MIR26B, and MIR196A2),snoRNAs (SNORD114-22, SNORD70, and SNORD114-31), pseudogenes (AC069366.1, RNU4ATAC11P, AC120057.1, NANOGP3, AC106038.2, TPT1P2, SDC4P, PKMP3, and VN2R3P), and protein-coding genes (AREG, GJB2, C12orf71, AC020909.2, S100A8, ZBED2, FABP7, and CYSLTR1). In addition, pathway analysis revealed that, among the most differentially methylated genes, STAT5A, RARA, MEF2D, MAP3K8, and THRA were the common regulators. It can be observed that HPV-induced warts involve a clear and unique epigenetic alteration to the host genome.

Rasheed K Ibdah,1 Laith N AL-Eitan,2 Nasr N Alrabadi,3 Ayah Y Almasri,2 Adan H Alnaamneh,2 Rame H Khasawneh,4 Mansour A Alghamdi5,6 1Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Hematopathology, King Hussein Medical Center (KHMC), Jordan Royal Medical Services (RMS), Amman, Jordan; 5Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia; 6Genomics and Personalized Medicine Unit,College of Medicine, King Khalid University, Abha, Saudi ArabiaCorrespondence: Laith N AL-EitanDepartment of Biotechnology and Genetic Engineering, Jordan University of Science and Technology. P.O.Box 3030, Irbid 22110, JordanTel +962-2-7201000 Ext. 23464Fax +962-2-7201071Email lneitan@just.eduBackground: The main objective of this study is sought to determine the impacts of PCSK9, WDR12, CDKN2A, and CXCL12 polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and stabilization phases of therapy.Methods: This study took place at the anticoagulation clinic at Queen Alia Heart Institute (QAHI) in Jordan. DNA samples were collected from 212 cardiovascular patients and 213 healthy controls. Genomic SNPs genotyping was conducted using the MassARRAY System at the Australian Genome Research Facility.Results: This study assessed 10 polymorphisms (rs11206510 within the PCSK9 gene, rs6725887 and rs7582720 within the WDR12 gene, rs4977574, rs10757278, and rs1333049 within the CDKN2A gene, rs2862116, rs7906426, rs1746048, and rs268322 within the CXCL12 gene) in 212 Jordanian cardiovascular patients. Carriers of CDKN2A rs1333049, rs10757278, and PCSK9 rs11206510 polymorphisms had an increased risk of resistance during the initiation phase of warfarin therapy compared to those who do not carry it, or those who are carrying one polymorphism only (P < 0.05), while carriers of CXCL12 rs7906426 polymorphism had similar increased risk but during the stabilization phase of warfarin therapy (P < 0.05).Conclusion: Carriers of CXCL12 rs2862116 polymorphism had an increased risk to be warfarin extensive responders compared to those with no or only one polymorphism (P = 0.01). However, the presence of PCSK9 rs11206510 polymorphism affects the warfarin maintenance doses (P ˃ 0.0001).Keywords: warfarin, cardiovascular disease, PCSK9, WDR12, CDKN2A, CXCL1

Background Cardiovascular disease is one of the most common causes of morbidity and mortality worldwide. Several cardiovascular diseases require therapy with warfarin, an anticoagulant with large interindividual variability resulting in dosing difficulties. The selected genes and their polymorphisms have been implicated in several Genome-Wide Association Study (GWAS) to be associated with cardiovascular disease. Objective The goal of this study is to discover if there are any associations between rs646776 of PSRC1, rs660240 and rs12740374 of CELSR2, and rs602633 of SORT1 to coronary heart disease (CHD) and warfarin dose variability in patients diagnosed with cardiovascular disease undergoing warfarin therapy. Methods The study was directed at the Queen Alia Hospital Anticoagulation Clinic in Amman, Jordan. DNA was extracted and genotyped using the Mass ARRAY™ system, statistical analysis was done using SPSS. Results The study found several associations between the selected SNPs with warfarin, but none with cardiovascular disease. All 4 studied SNPs were found to be correlated to warfarin sensitivity during the stabilization phase except rs602633 and with warfarin dose variability at the initiation phase. CELSR2 SNPs also showed association with dose variability during the stabilization phase. Also, rs646776 and rs12740374 were linked to warfarin sensitivity over the initiation phase. Only rs602633 was associated with INR treatment outcomes. Conclusion The findings presented in this study found new pharmacogenomic associations for warfarin, that warrant further research in the field of genotype-guided warfarin dosing.

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).

Objective In this study, we aimed to explore the relationship between five selected proinflammatory and immune-mediated genes (TNF rs1800629G>A, rs361525G>A, rs1799964T>C, LTA rs1800683G>A, rs909253A>G, TNFAIP8 rs1042541C>T, LEPR rs1327118G>C, and LEP rs2167270G>A) and the risk and overall survival of DLBCL patients within the Jordanian Arab population. Methods One hundred twenty-five patients (125) diagnosed with DLBCL at the King Abdullah University Hospital (KAUH) between 2013 and 2018 and 238 healthy cancer-free control subjects with similar geographic and ethnic backgrounds to the patients were included in the study. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissues of the subjects and from peripheral blood samples of the controls. The Sequenom MassARRAY® sequencer system (iPLEX GOLD) was used. The analyses included assessments of population variability and survival. Results Our study showed significant differences in the distribution of the studied polymorphisms of DLBCL between the patients and controls for TNF rs1800629G>A, LTA rs909253 G>A and LEP rs2167270 G>A. TNF rs1800629G>A (p = 0.01), in which the G allele harbors a higher risk of DLBCL (GG and GA genotypes when compared with AA genotype) (p = 0.044). The LTA rs909253 A>G polymorphism is associated with a higher risk of DLBCL in the allelic model (p = .004). LEP rs2167270 G>A polymorphism is associated with a decreased risk of DLBCL in the recessive mode models (p = .03). Subjects with the dominant model for TNF-a rs1799964 (TT genotype in comparison with the combined TT/TC genotype) and patients with the homozygous genotype (GG) of rs361525 have better overall survival rates. Conclusion Our results confirmed the diversity and the heterogeneity of the disease. Although the study has a limitation because of its relatively small size, it clearly emphasizes the significance of ancestry and genetic composition as the determinants of DLBCL risk and behavior. .

Synthetic cannabinoids (SCs) are a group of newly-developed drugs that bind and activate endocannabinoid system receptors. Angiogenesis is a biological process in which new blood vessels are formed from preexistent blood vessels. It plays a vital role in tissue growth, wound healing, and embryogenesis. This study aims to investigate the effects of the synthetic cannabinoid XLR-11 on specific cellular functions such as viability and angiogenesis in vitro. Human brain microvascular endothelial cells (HBMECs) were cultured in DMEM/F12 medium supplemented with an endothelial cell growth kit. The MTT assay was used to investigate the viability of endothelial cells. An endothelial cell migration assay was used to investigate migration ability, while a tube formation assay was used to investigate the angiogenic capacity of the endothelial cells. XLR-11 was found to enhance the viability of HBMECs. Moreover, the migration rate and angiogenic capacity significantly increased in the presence of various concentrations of XLR-11 compared to the control. The current study shows that XLR-11 increases the viability of human brain microvascular endothelial cells and enhances angiogenesis in the brain in vitro, suggesting that XLR-11 could potentially be used as a therapeutic angiogenic drug in human brain injury treatment.

Background Profiling rare variants in isolated populations can significantly clarify and understand the development of a clinically relevant process. Therefore, leading to a better identifying novel targeted treatment. Objective This study aimed to determine the allele frequencies of 56 single nucleotide polymorphisms (SNPs) within several important pharmacogenes. Methods This study consisted of 166 unrelated subjects from a genetically isolated group (Chechen) who were living in Jordan. In this study, the distribution of the variants among Chechen was compared to other ethnic groups available at two databases (Genome 1000 and (ExAC)). The frequency of genotypes and alleles was calculated and tested using the chi-square test and the Hardy-Weinberg equilibrium equation (HWE). Results Our results revealed that the distribution of allele frequencies within different pharmacogenes among Chechen showed different similarities with other populations. The CEU and TSI showed the highest resemblance with the Chechen population (75% similarity), in contrast to LWK which had the lowest similarity (30%). Conclusion This study sheds light on clinically relevant SNPs to enhance medical research and apply pharmacogenomics in clinical settings.

Background: Differences in individual responses to the same medications remarkably differ among populations. A number of genes that play integral roles in drug responses have been designated as very important pharmacogenes (VIP), as they are responsible for differences in drug safety, efficacy, and adverse drug reactions among certain ethnic groups. Identifying the polymorphic distribution of VIP in a range of ethnic groups will be conducive to population-based personalized medicine. Objective: The aim of the current study is to identify the polymorphic distribution of VIP regarding the Chechen minority group from Jordan and compare their allele frequencies with other populations. Methods: A total of 131 unrelated Chechen individuals from Jordan were randomly recruited for blood collection. Identification of allelic and genotypic frequencies of eleven VIP variants within the genes of interest (ABCB1, VDR and TPMT) was carried out by means of the MassARRAY®System (iPLEX GOLD). Results: Within ABCB1, we found that the minor allele frequencies of the rs1128503 (A: 0.43), rs2032582 (A: 0.43), rs1045642 (A: 0.43). For VDR, the minor allele frequencies of rs11568820 (T: 0.18), rs1540339 (T: 0.30), rs1544410 (T: 0.41), rs2228570 (T: 0.24), rs3782905 (C: 0.28) and rs7975232 (C: 0.45). Finally, the minor allele frequencies for the TPMT rs1142345 and rs1800460 polymorphisms were found to be (C: 0.02) and (T: 0.01), respectively. Conclusion: Significant differences in allelic frequencies of eleven ABCB1, VDR and TPMT VIP variants were found between Jordanian Chechens and other populations. In our study, most populations that are similar to Chechens are those from South Asian, European (Finnish) and European, including: Utah residents with Northern and Western European ancestry, Toscani in Italia, Mexican ancestry in Los Angeles and Circassian from Jordan. The level of similarity between Chechens and those populations means that they might have shared high levels of gene flow in the past. The results obtained in this study will contribute to the worldwide pharmacogenomic databases and provide valuable information for future studies and better individualized treatments.

Introduction Among the Jordanian population, brain tumors are the tenth most common type of cancers in both males and females, comprising 2.8% of all newly diagnosed neoplasms. Diffuse gliomas are the most prevalent and the most aggressive primary brain tumors in adults. The incidence of diffuse gliomas varies among different populations; this variation is partially linked to genetic polymorphisms. The purpose of the study is to examine the association between (BRCA1 rs799917G>A, rs1799966T>C, EXO1 rs1047840G>A, EME1 rs12450550T>C, ERCC2 rs13181T>G, rs1799793C>T, and XRCC1 rs1799782G>A) DNA repair gene polymorphisms and glioblastoma multiforme (GBM) susceptibility, and survival in the Jordanian Arab population. Methods Eighty-four patients diagnosed with glioblastoma multiforme at the King Abdullah University Hospital (KAUH) between 2013 and 2018 and 225 healthy cancer-free control subjects with similar geographic and ethnic backgrounds to the patients were included in the study. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissues of the subjects. The Sequenom MassARRAY® sequencer system (iPLEX GOLD) was used. The analyses included assessments of population variability and survival. Results This study is the first to address the relationship between BRCA1 rs1799966 and rs799917 SNP, and the risk of GBM among the Arab Jordanian population. The findings of the study show that BRCA1 rs799917 is associated with decreased risk of GBM in the recessive model (AA vs G/G-A/G: OR, 0.46, 95% CI, 0.26-0.82, p=0.01) and the same SNP is associated with increased risk of GBM in the overdominant model (AG vs G/G-A/A: OR, 1.72, 95% CI, 1.02-2.89, p=0.04).

Objective To investigate the genotypic and allelic association of Src homology 2 B adapter protein 1 (SH2B1) gene polymorphisms with type 2 diabetes mellitus (T2DM) in Jordanian patients. Patients and Methods Three hundred patients were screened, but only 200 adult Jordanian patients diagnosed with T2DM (53.5% male and 46.5% female) have participated in this study. Blood samples were collected from both patients and healthy individuals for DNA extraction according to well-established procedures. Exon 1 and exon 9 of the SH2B1 gene were sequenced using an efficient and sensitive DNA sequencing method in order to identify specific single nucleotide polymorphisms (SNPs) in the SH2B1 gene associated with T2DM. Genetic and haplotype correlation analysis was performed for the chosen SNPs to detect any association if existent. In addition, SNPStats Web Tool and Hardy-Weinberg equilibrium (HWE) analyses for the genotype distribution were used. The significance was determined according to the P-value, and the level of significance taken as P 0.05. Also, the patient's characteristics and clinical data about all participants were mentioned. Results Two novel variations were present in the SH2B1 gene in Jordanian patients with T2DM: c.827C>G and c.2026G>A, and previously reported five SNPs: rs146946750, rs565131715, rs370302573, rs143212778, rs200470848. Our results showed a strong genetic association of rs565131715 SNP polymorphism within the SH2B1 gene in T2DM patients (χ2 test, P < 0.001). Additionally, rs143212778 SNP presented a genetic correlation with T2DM patients (χ2 test, P = 0.035) as compared to control individuals. GTACG haplotype of SH2B1 has a highly significant association with responders (P< 0.0001). Conclusion Our findings indicated a strong association between the rs565131715 polymorphism and the risk of T2DM among the Jordanian population. Moreover, our data showed that the rs143212778 polymorphism significantly elevated the danger of T2DM among this population. This study reveals the first data regarding the SH2B1 gene polymorphisms in Jordanian patients of Arab descent with diabetes.

Magnetism is one of the physical methods affecting water properties. It is considered as an environmental factor that plays a role in the physiological and biochemical reactions. A hydroponic experiment was conducted using four types of treated water (distilled water, magnetically treated distilled water, magnetically treated tap water, and tap water). Tobacco plants (Nicotiana tabacum var. Turkish) were placed in a growth chamber for three weeks. Plants irrigated with magnetically treated distilled water had a significant increase in the physiological parameters including shoot height and root length (P

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.

Epigenetic alteration of host DNA is a common occurrence in both low- and high-risk human papillomavirus (HPV) infection. Although changes in promoter methylation have been widely studied in HPV-associated cancers, they have not been the subject of much investigation in HPV-induced warts, which are a temporary manifestation of HPV infection. The present study sought to examine the differences in promoter methylation between warts and normal skin. To achieve this, DNA was extracted from 24 paired wart and normal skin samples and inputted into the Infinium MethylationEPIC BeadChip microarray. Differential methylation analysis revealed a clear pattern of hyper- and hypomethylation in warts compared to normal skin, and the most differentially methylated promoters were found within the EIF3EP2, CYSLTR1, C10orf99, KRT6B, LAMA4, and H3F3B genes as well as the C9orf30 pseudogene. Moreover, pathway analysis showed that the H3F3A, CDKN1A, and MAPK13 genes were the most common regulators among the most differentially methylated promoters. Since the tissue samples were excised from active warts, however, this differential methylation could either be a cellular response to HPV infection or an HPV-driven process to establish the wart and/or promote disease progression. Conclusively, it is apparent that HPV infection alters the methylation status of certain genes to possibly initiate the formation of a wart and maintain its presence.

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.

Background Genetic predisposition to breast cancer (BC) has been extensively explored to achieve an enhanced understanding of the biology of BC. Targeting candidate genes to screen different genetic variants such as RAD51 gene that plays a critical role in DNA repair pathways including the double-strand break repair system is an important task. Aim To study several single nucleotide polymorphisms (SNPs) within RAD51-UTR gene and to find their relationship with BC risk and prognosis among Jordanian females. Materials and methods In this case-control study, DNA sequencing technique was used to screen SNPs within the untranslated region (UTR) of RAD51 in 206 cases and 185 controls and the resulting data were statistically analyzed using different types of genetic analyses. Patients' clinical and pathological features were obtained from their medical records to perform genotype-phenotype association analysis. Results Our findings show a significant association between both SNPs rs528590644, rs1801320 and BC risk (p = 0.016). We estimated the correlation between many of BC prognostic factors and BC risk, and we found an association between rs1801321 and age at first menstruation (p = 0.032) in addition to a strong correlation between age at BC diagnosis and rs1801320 (p = 0.008). Conclusion RAD51-UTR polymorphisms may be involved in BC development and progression.

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.

Background: It has been suggested that genetic variation within candidate pharmacogenes contributes to the differences in drug safety and efficacy as well as risk of adverse drug reactions among different ethnic groups. Illustrating the polymorphic distribution of Very Important Pharmacogenes (VIPs) in various ethnic groups will contribute to the development of personalized medicine for those populations. Objective: The present study aimed to identify the polymorphic distribution of VIPs in the Circassian subpopulation of Jordan and compare their allele frequencies with those of other populations. Methods: A total of 130 healthy and unrelated Circassian adults from Jordan were randomly recruited and genotyped for eleven VIP variants within the thiopurine S-methyltransferase (TPMT), ATP-binding cassette, sub-family B, member 1 (ABCB1), and vitamin D receptor (VDR) genes via Sequenom’s MassARRAY® genotyping platform (iPLEX GOLD). Results: Our data on the allelic frequencies of the investigated VIP variants were compared to those of 18 other populations, comprising 11 HapMap populations, 6 Exome Aggregation Consortium populations, and the Chechen- Jordanian population from Jordan. Circassian-Jordanians were found to most resemble the African, Chechen- Jordanian, European (Finnish), European (non-Finnish), and South-Asian populations. Conclusion: Circassians from Jordan significantly differ from other populations in terms of the allelic frequencies of selected VIP variants. The present findings constitute the first set of pharmacogenetic data for Circassian population from Jordan, providing a basis for safe drug administration that may be useful in diagnosing and treating diseases in this ethnic group.

Purpose Genetic predisposition to disease has become one of the most investigated risk factors in recent years, and breast cancer (BC) is no exception. In this study, we investigated specific genetic variants of three candidate genes belonging to the glutathione-S-transferase superfamily that have been implicated in increased risk of cancers. Materials and methods This case-control study comprised 241 Jordanian women who were diagnosed with BC in addition to 219 matched controls. Gel electrophoresis of PCR products was used to visualize and genotype both the GSTM1 and GSTT1 genes, while PCR-RFLP was employed to genotype the rs1695 of the GSTP1 gene. Results Our findings did not reveal any correlation between the investigated polymorphisms of GST genes and BC risk among Jordanian women. Otherwise, the combination of GSTM1 entire gene deletion and (GG) genotype of GSTP1 polymorphism (rs1695) was significantly associated with BC with p-value

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.

Purpose Breast cancer (BC) is a complex disease that is governed by several different environmental and inherited factors. There are many genes have been linked with BC development by screening specific genetic variants within these genes. In this study, we aim to investigate the correlation between Variable Number Tandem Repeat (VNTR) in XRCC5 gene and BC. Materials and methods Polymerase Chain Reaction (PCR) and Gel electrophoresis were used to genotype the XRCC5 gene polymorphism in 200 cases with breast cancer and 200 healthy individuals. All participants were Jordanian women from Arab descents. Clinical and pathological characteristics for BC patients were summarized and categorized according to their medical records. Results In this study, we found a strong correlation between the VNTR polymorphism in the XRCC5 gene and BC risk (P-value

Backgrounds Breast cancer (BC) is one of the most widespread cancers globally. Understanding the etiology of BC may help in determining the various risk factors involved in its malignancy. Certain genetic mutations are considered to play a key role in increasing the risk of BC. Objectives In this study, we explored the correlation between a variable number tandem repeat (VNTR) polymorphism in the IL-4 gene and BC. Methods PCR and subsequent gel electrophoresis were used to genotype this variant in 360 Jordanian women (180 BC patients and 180 controls). In addition, phenotype-genotype analysis was carried out. Results Our findings illustrate that there is no significant relationship between the variant genotypes in the IL-4 gene and BC among Jordanian females. Other than body mass index and tumor differentiation (p< 0.05), none of the clinical and pathological parameters of BC patients exhibited any association with the variant genotypes. Conclusions From this study, we propose that the IL-4 genetic variant does not impact BC development and progression but that it could influence the disease prognosis.

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.

The main objective of this study is to assess the effects of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness in a Jordanian population during the stabilization phase of treatment. This study was conducted at the Queen Alia Heart Institute (QAHI) anticoagulation clinic in Amman, Jordan. We assessed three CYP2C9 (rs1799853, rs1057910, rs4086116) and four VKORC1 (rs10871454, rs8050894, rs9934438, rs17708472) polymorphisms in 139 Jordanian cardiovascular patients. Demographic and clinical data were also collected. Of the 139 patients in the cohort, 80% had the VKORC1 polymorphisms rs10871454 and rs9934438, while 22.3% and 24.5% of patients had the rs1799853 and rs1057910 CYP2C9 alleles, respectively. Carriers of the CYP2C9 polymorphisms rs1057910 and rs4086116 had an increased risk of warfarin sensitivity compared to subjects with no or only one polymorphism. Similarly, carriers of all four VKORC1 variants had an increased risk of warfarin sensitivity (over anticoagulation) compared to those with no or only one polymorphism. Patients with a CYP2C9 or VKORC1 polymorphism required significantly lower doses than patients with no polymorphisms. The presence of any of CYP2C9 or VKORC1 polymorphisms is associated with sensitivity to warfarin during the stabilization period. Being a CYP2C9 or VKORC1 polymorphism carrier is associated with a variation in doses required to achieve the therapeutic INR compared to non-carrier patients. Keywords: CYP2C9, VKORC1, Warfarin, Warfarin maintenance phase of therapy, INR