Factors affecting SARS-CoV-2 variant distribution in military hospitals in Jordan.

The pandemic caused by SARS-CoV-2 has prompted a collaborative global effort to contain viral spread and improve health outcomes for those infected. The tracking of SARS-CoV-2 variants since the first sequence was published in January 2020 is an important part understanding the pandemic. There is limited data regarding SARS-CoV-2 circulation in Jordan. In this study we determined the prevalence of genetic variants of SARS-CoV-2 during June-September 2021 by sequencing the full genome of 213 viral samples from Jordanian Royal Medical Services military hospitals. Our analysis revealed the presence of 33 variants, with (B.1.617.2.AY.106) as the predominate strain. Six variants were present at a prevalence greater than 2%((B.1.617.2.AY.106), 52.8%; Delta (B.1.617.2), 7.0%; (B.1.617.2.AY.34.1), 5.6%;(B.1.617.2.AY.44), 2.8%; (B.1.617.2.AY.121), 2.33%; (B.1.617.2.AY.102), 2.33%). Variant prevalence varied significantly by region and (B.1.617.2.AY.106) variant tended to be associated with mild to moderate symptoms, on the other hand other variants were asymptomatic. We did not find significant associations of variants with other factors such as age, gender or vaccination status. These data help us to understand the occurrence of new variants in Jordan, their geographic distribution, and associations with demographic variables, vaccination status, and symptom severity. The sustained circulation of SARS-CoV-2 continues to lead to novel variant emergence. These findings highlight the need to continue tracking new variants, monitor the dynamics of variant prevalence, and future efforts will guide prevention, vaccination, and control strategies.

Epidemiology of human brucellosis in military hospitals in Jordan: A five-year study.

INTRODUCTION: Brucellosis is a zoonotic disease with significant impacts on livestock and human health. It is a severe community health burden in the Middle East with an estimated 2000 times higher prevalence than in North America and Western Europe. To date, there are limited studies on human brucellosis and risk factors for infection in Jordan. Our study aimed to analyze documented brucellosis cases in Jordan and use geographic and socio-demographic data to better understand its prevalence and transmission. METHODOLOGY: This retrospective study examined electronic medical records describing 1,497 cases of febrile illness that were tested for brucellosis at Royal Medical Services hospitals between 2016 and 2020. A total of 465 confirmed brucellosis cases, aged 0 to 80 years were included. Serum samples were screened for anti-Brucella antibodies, and positive samples were additionally tested for antibody titer using the Wright tube agglutination test. RESULTS: Our results showed that 31.1% (456/1497) of the febrile diseases were brucellosis. We found that young adults and working age, northern governorates, rural location of residency, occupations involving regular contact with livestock, and Spring/Summer season were highly significant as risk factors. Seropositivity was highest among dairy factory workers with 64.4%. CONCLUSIONS: This study adds to our understanding of human brucellosis in Jordan and its impact on public health. These data will be useful in the prevention of brucellosis and will inform reliable disease control policies.

Variants in CDHR3, CACNAC1, and LTA Genes Predisposing Sensitivity and Response to Warfarin in Patients with Cardiovascular Disease.

INTRODUCTION: Warfarin has been in use for more than 60 years; however, it has serious side effects including major bleeding. The high interpatient variability in the required dose impacts the sensitivity and responsiveness to warfarin in different patients. This study aims to assess the influence of CDHR3, CACNAC1, and LTA gene polymorphisms on the variability of warfarin dose requirements and susceptibility to coronary heart disease in the Jordanian population. METHODS: This study was conducted in the anti-coagulation clinic in Queen Alia Heart Institute in Amman, with 212 patients in total. Three SNPs were genotyped within CDHR3 (rs10270308), CACNAC1 (rs216013), and LTA (rs1041981) genes. RESULTS: Our findings revealed that patients with LTA polymorphism are more prone to warfarin sensitivity than others. Furthermore, carriers of the LTA polymorphism needed a lower initial dose of warfarin and are associated with less variation in doses required to achieve target INR. CONCLUSION: The current study could help in understanding the role of genetic variability in warfarin dosing and matching patients to different treatment options. Clinical applications of these findings for warfarin treatment may also contribute to improving the efficacy and safety of warfarin treatment in Jordanian patients with cardiovascular disease.

Influence of CYP4F2, ApoE, and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility to cardiovascular disease in Jordan.

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.

Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity.

BACKGROUND: 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).

Influence of PSRC1, CELSR2, and SORT1 Gene Polymorphisms on the Variability of Warfarin Dosage and Susceptibility to Cardiovascular Disease.

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.

Influence of SH2B3, MTHFD1L, GGCX, and ITGB3 Gene Polymorphisms on theVariability on Warfarin Dosage Requirements and Susceptibility to CVD in the Jordanian Population.

The purpose of this study was to investigate the effects of the SH2B3, MTHFD1L, GGCX, and ITGB3 gene variants on the efficacy of warfarin treatment and its effects on the risk of cardiovascular disorders in Jordanian patients. The selected genes and their polymorphisms are involved in many Genome-Wide Association Study (GWAS) associated with cardiovascular disease and the variability of warfarin therapy. The current study conducted a genetic association and pharmacogenetics study in (212) Jordanian cardiovascular patients treated with warfarin and (213) healthy controls. DNA extraction and the Mass ARRAY™ system were used to genotype ten selected polymorphisms within four genes (SH2B3, MTHFD1L, GGCX, and ITGB3). This study confirmed a genetic association of MTHFD1L rs6922269 Single Nucleotide Polymorphism (SNP) with warfarin sensitivity during the initial and stabilization phases of treatment. Moreover, this SNP showed significant differences in the initial and maintenance doses of warfarin. This study also found an association between the genetic haplotypes (AGC and GAT) within the SH2B3 gene and responsiveness to warfarin. However, possession of an MTHFD1L rs491552 variant allele was found to affect the outcome measure of the international normalized ratio (INR) during the stabilization phase of warfarin treatment. In contrast, there was no association between all selected SNPs and susceptibility to cardiovascular disorders. This study extends the current understanding of the high variability of the warfarin response, including variability in dose requirements and susceptibility to cardiovascular disease in the Jordanian-Arab population. Other studies on a larger sample and in different ethnic groups could help to better understand the pharmacogenetics of warfarin and its application in personalized medicine.

Novel mutations in the SMPD1 gene in Jordanian children with Acid sphingomyelinase deficiency (Niemann-Pick types A and B).

Acid sphingomyelinase (ASM) deficiency (ASMD) is a spectrum that includes Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). ASMD is characterized by intracellular accumulation of unesterified cholesterol and gangliosides within the endosomal-lysosomal system. It is caused by different mutations in SMPD1 gene that result in reduction or complete absence of acid sphingomyelinase activity in the cells. Herein, four unrelated consanguineous families with two NPD A and three NPD B patients were assessed for their genotypes via sequencing of the SMPD1 gene and their acid sphingomyelinase enzymatic activity. Among the eight identified mutations, three were novel and reported for the first time in Jordanian families (c.120_131delGCTGGCGCTGGC or c.132_143delGCTGGCGCTGGC, c.1758T > G, and c.1344T > A). All the patients displayed ASM activity lower than 1.3 µmol/l/h (P < 0.001). Genotyping and enzymatic assessment might play a significant role in disease identification in people at risk to facilitate genetic counseling in the future.

Identification and Characterization of BTD Gene Mutations in Jordanian Children with Biotinidase Deficiency.

Biotinidase deficiency is an autosomal recessive metabolic disorder whose diagnosis currently depends on clinical symptoms and a biotinidase enzyme assay. This study aimed to investigate the mutational status and enzymatic activity of biotinidase deficiency in seven unrelated Jordanian families including 10 patients and 17 healthy family members. Amplified DNA was analyzed by the automated Sanger sequencing method, and the enzymatic assay was performed using a colorimetric assessment. Biotinidase level was significantly lower (p < 0.001) in BTD children compare to their non-affected family members. Genetic sequencing revealed six different mutations in Jordanian patients. One mutation was novel and located in exon 4, which could be a prevalent mutation for biotinidase deficiency in the Jordanian population. Identification of these common mutations and combing the enzymatic activity with genotypic data will help clinicians with regard to better genetic counseling and management through implementing prevention programs in the future.

Total and Specific Immunoglobulin E for Detection of Most Prevalent Aeroallergens in a Jordanian Cohort.

INTRODUCTION: Allergies are defined as an immune response to non-microbial environmental antigens (allergens) that involve TH2 cells, mast cells, eosinophils and immunoglobulin E (IgE). Atopic disorders such as urticaria, asthma, hay fever, and eczema exhibit a strong familial predisposition and specific IgE-mediated reaction after exposure to the allergens. Aeroallergens involved in the hypersensitivity reactions include pollens, animal dander, fungal spores and house dust mite. Frequency and type of aeroallergens vary in different countries based on climate, vegetation and geographic areas. AIM: Due to increased prevalence of allergic diseases, in vitro diagnostic tests are commonly utilized in our area. The aim of our study is to evaluate the association between total and specific IgE and to study frequency of different aeroallergens in the population. METHODS: The study was conducted in a time period between 1/12/2017 and 15/11/2018 at King Hussein Medical Center, Amman, Jordan. A total of 80 patients with symptoms of allergic disorders were included, ages of individual's ranged between 1 year and 77 years, 58.8 % (n=47) of which male and 41.2 % (n=33) female. Blood samples from all patients were collected into a 10 ml gel separator (with clot activator) tubes and tested for total IgE and specific IgE. RESULTS: A total of 80 patients aged 1-77 years were divided into 4 groups depending on the normal value of total IgE as follow: 1-5 years, 6-9 years, 10-15 years, and adult. A total of 43(53.75%) patients exhibited elevated total IgE level, and 37(46.25%) had normal level. 41(51.2%) patients had elevated total IgE and positive specific IgE. The sensitivity and specificity of total IgE when using specific IgE as standard test was 77.4% and 92.5% respectively. The accuracy rate of the total IgE test was 82.5%. The most common aeroallergens were dermatophagoides pteronyssinus (13.6%), followed by grass mix (12.8). CONCLUSION: Testing of specific IgE is an essential procedure that helps to detect the cause of allergy. Although negative specific IgE could not exclude allergen sensitization due to limitations of detection method and allergen selection, and positive total and specific IgE indicate probability of sensitization.

The influence of an IL-4 variable number tandem repeat (VNTR) polymorphism on breast cancer susceptibility.

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.

Association Of GSTM1, GSTT1 And GSTP1 Polymorphisms With Breast Cancer Among Jordanian Women.

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 <0.05 (i.e. p-value was not significant after correcting for multiple comparison). CONCLUSION: We suggest that the interaction between GSTM1 polymorphism and rs1695 of GSTP1 may influence BC development and progression among Jordanian women. More epidemiological studies are needed to provide a baseline for the underlying role of GSTs polymorphisms in tumorigenesis.

Correlation between Candidate Single Nucleotide Variants and Several Clinicopathological Risk Factors Related to Breast Cancer in Jordanian Women: A Genotype-Phenotype Study.

This study aim to investigate the association of breast cancer risk and prognostic factors with single nucleotide variants of the BRCA1, BRCA2, DAPK1, MMP9, TOX3, and TP53 genes in Jordanian women. Blood samples were collected from 230 Jordanian breast cancer patients for use in DNA extraction followed by genotyping and subsequent statistical analysis. We found that two single nucleotide variants (SNVs) of the BRCA2 gene, namely rs1799944 and rs766173, were significantly associated with breastfeeding status. Likewise, the rs11141901 and rs1041326 SNVs of the DAPK1 gene were linked with co-morbidity (p-value = 0.002) and family history of BC (p-value = 0.015), while the rs1045042 SNV of the same gene was associated with both allergy (p-value = 0.001) and family history of BC (p-value = 0.02). Tumor differentiation was correlated with the DAPK1 SNVs rs11141901 (p-value = 0.041) and rs1041326 (p-value = 0.005). Additionally, the rs2250889 SNV of the MMP9 gene was significantly associated with HER2 status, whereas the TP53 SNVs rs12951053 and rs1042522 were associated with age at menarche (p-value = 0.043) and breastfeeding status (p-value = 0.013), respectively. In contrast, the TP53 SNV rs2287497 was significantly linked to age at first pregnancy (p-value = 0.001), smoking (p-value = 0.041), and axillary lymph node status (p-value = 6e-4). No such association was found for the BRCA1 and TOX3 SNVs. The current findings suggest significant associations between certain SNVs and breast cancer risk and prognosis in Jordanian women.

Association of CYP gene polymorphisms with breast cancer risk and prognostic factors in the Jordanian population.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in several CYP genes have been associated with altered breast cancer (BC) risk in different populations. Despite this, there is a dearth of information on the roles of these SNPs in Jordanian BC patients. Therefore, this study aims to determine if there is any single nucleotide polymorphism (SNP) within CYP19A1, CYP2C19, CYP2C9, CYP1B1, CYP3A4, and CYP1A2 genes associated with BC in the Jordanian population. In addition, this work investigates the association between selected BC prognostic factors and variants of the aforementioned CYP candidate genes. METHODS: Blood samples were withdrawn from 221 BC patients and 218 healthy volunteers recruited from the Jordanian population. Genomic DNA was withdrawn and, after quantification and quality control, was genotyped using the Sequenom MassARRAY® system (iPLEX GOLD). Statistical analysis was then carried out to assess allelic and genotypic frequencies as well as genetic association between cases and controls. RESULTS: The CYP19A1 SNP rs7176005 (p < 0.0045) and the CYP1A2 SNP rs762551 (p = 0.004) were significantly associated with BC risk. However, no such association was found for the screened SNPs of the CYP2C9, CYP1B1, CYP2C19 and CYP3A4 genes. Regarding the prognostic factors of BC, several of the screened SNPs were associated with different pathological and clinical features. CONCLUSIONS: Certain CYP genes, particularly CYP19A1 and CYP1A2, were associated with BC risk and development in the Jordanian population.

Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients.

Breast cancer pharmacogenetics is increasingly being explored due to chemotherapy resistance among certain classes of patients. The ATP binding cassette (ABC) transporter genes have been previously implicated in breast cancer progression and drug response. In the present study, single nucleotide polymorphisms (SNPs) from the ABCC1, ABCC2, ABCB1, and ABCG2 genes were screened in breast cancer patients and healthy volunteers from the Jordanian-Arab population. Only the ABCB1 SNPs showed a significant association with BC in Jordanian-Arab patients, and the ABCB1 SNP rs2032582 exhibited a strong genotypic association with BC. With regard to the clinical characteristics of BC, the ABCC2 SNPs rs2273697 and rs717620 were found to be significantly associated with age at breast cancer diagnosis and breastfeeding status, while the ABCB1 SNP rs1045642 was significantly associated with age at breast cancer diagnosis. In terms of pathological characteristics, the ABCC1 SNP rs35628 and the ABCB1 SNP rs2032582 were significantly associated with tumor size, the ABCC2 SNP rs2273697 was significantly associated with estrogen receptor status, and the ABCG2 SNP rs2231142 was significantly associated with axillary lymph node status. In this current study, we assume that significant genetic variants within the ABC superfamily may increase the risk of breast cancer among Jordanian women. Furthermore, these variants might be responsible for worse BC prognosis.

Effects of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness during the stabilization phase of therapy.

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.

Association between ESR1, ESR2, HER2, UGT1A4, and UGT2B7 polymorphisms and breast Cancer in Jordan: a case-control study.

BACKGROUND: Breast cancer risk, development, and treatment are influenced by genetic variation in certain genes, namely those involved in cell proliferation, tumor suppression, and drug metabolism. In turn, the relevance of the aforementioned genetic variation to cancer depends on the ethnic group in question, highlighting the need for population-specific association studies. Therefore, the objective of the present study was to investigate the association between certain ESR1, ESR2, HER2, UGT1A4, and UGT2B7 single nucleotide polymorphisms and breast cancer. METHODS: Blood samples were collected from 437 Jordanian-Arab breast cancer patients and healthy volunteers and subject to genotyping using the Sequenom MassARRAY® system (iPLEX GOLD). RESULTS: Our findings show a significant association between breast cancer and the allelic (P = 0.02486879) and genotypic (P = 0.04793066) frequencies of the ESR1 polymorphism rs3798577, a result which was confirmed in different genetic models. No other investigated polymorphism showed a significant association with breast cancer itself in Jordanian Arabs, but the Rare Hz (GG) vs Het (AG) genetic model revealed an association of the disease with the ESR1 polymorphism rs3798577. However, several associations were found between certain polymorphisms and breast cancer's prognostic factors. CONCLUSION: This study suggests that certain polymorphisms may increase the risk of breast cancer in the Jordanian-Arab population. Future research and clinical translation could incorporate the current results in preventative breast cancer approaches tailored for Jordanian-Arab patients.

Genetic association of XRCC5 gene polymorphisms with breast cancer among Jordanian women.

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<0.0001). Remarkably, three different genotypes (2R\2R, 3R\2R and 3R\3R) showed significant association with BC (P-value<0.0001). This study also reported a significant difference in the distribution of allele frequencies between BC patients and healthy individuals (3R; P-value<0.0001 and 2R; P-value<0.001). However, we propose that VNTR of XRCC5 gene did not interfere with BC prognosis. CONCLUSION: We speculate that the VNTR of XRCC5 gene may influence BC development. More investigations are needed in this regard to clarify the underlying role of the XRCC5 genetic variant in tumorgenesis including BC development.

Impact of CYP2C9 and VKORC1 Polymorphisms on Warfarin Sensitivity and Responsiveness in Jordanian Cardiovascular Patients during the Initiation Therapy.

Warfarin is an oral anticoagulant frequently used in the treatment of different cardiovascular diseases. Genetic polymorphisms in the CYP2C9 and VKORC1 genes have produced variants with altered catalytic properties. A total of 212 cardiovascular patients were genotyped for 17 Single Nucleotide Polymorphisms (SNPs) within the CYP2C9 and VKORC1 genes. This study confirmed a genetic association of the CYP2C9*3 and VKORC1 rs10871454, rs8050894, rs9934438, and rs17708472 SNPs with warfarin sensitivity. This study also found an association between CYP2C9 and VKORC1 genetic haplotype blocks and warfarin sensitivity. The initial warfarin dose was significantly related to the CYP2C9*3 polymorphism and the four VKORC1 SNPs (p < 0.001). There were significant associations between rs4086116 SNP and TAT haplotype within CYP2C9 gene and rs17708472 SNP and CCGG haplotype within VKORC1 gene and warfarin responsiveness. However, possessing a VKORC1 variant allele was found to affect the international normalized ratio (INR) outcomes during initiation of warfarin therapy. In contrast, there was a loose association between the CYP2C9 variant and INR measurements. These findings can enhance the current understanding of the great variability in response to warfarin treatment in Arabs.

A Novel Mitochondrial DNA Deletion in Patient with Pearson Syndrome.

INTRODUCTION: Arteriovenous Pearson syndrome is a very rare multisystemic mitochondrial disease characterized by sideroblastic anemia and exocrine pancreatic insufficiency. It is usually fatal in infancy. CASE REPORT: We reported a four-month-old infant presented with fever and pancytopenia. Bone marrow examination showed hypoplastic changes and sideroblastic features. Molecular Study showed a novel hetroplasmic mitochondrial deletions (m. 10760 -m. 15889+) in multiple genes (ND4,ND5,ND6, CYTB). In our patient the pathogenic mutation was 5.1 kb heteroplasmic deletions in multiple genes that are important and crucial for intact oxidative phosphorylation pathway and ATP production in the mitochondrial DNA. This mutation was not reported in literature including the mitomap.org website (which was last edited on Nov 30, 2017 and accessed on Jan 13, 2018).