Family and case-control genetic study of MSX1 polymorphisms in peg-shaped teeth Jordanian population.

BACKGROUND: This study aimed to investigate the genetic association of specific Single Nucleotide Polymorphisms (SNPs) within the muscle segment homeobox gene 1 (MSX1) with susceptibility to the peg-shaped teeth in 36 Jordanian Arab families and case-control samples in the Jordanian Arab population. METHODS: This cohort involved 108 individuals (36 trios families), which were used for family-based genetic study. Additionally, 56 patients and 57 controls were used for case-control study. Genomic DNA samples from both families and case-control were extracted according to distinguished processes. Then, polymerase chain reaction technique (PCR) was conducted using specific primers for the axons of the MSX1. Moreover, DNA sequencing genotyping method analysis of SNPs was used to detect specified SNPs in the MSX1 linked with peg-shaped teeth. Hardy-Weinberg Equilibrium and Chi-square were used to evaluate the data quality and the presence of any genotypic error. In addition, Transmission Disequilibrium Test (TDT) was used identify family-based association in which trios of parents and proband are used. RESULTS: The results of this study showed fourteen polymorphic sites in this gene, eight of them (rs121913129, rs104893852, rs104893853, rs121913130, rs104893850, rs1095, rs3775261, and rs1042484) were none-polymorphic. Meanwhile, the minor allele frequencies of the rest of the SNPs were polymorphic (rs8670, rs12532, rs3821949, rs4464513, rs1907998, and rs6446693). However, none of these SNPs were associated with peg-shaped teeth. Moreover, the haplotype genetic analysis revealed that there was no genetic association with peg-shaped teeth disorder susceptibility (P > 0.05) in the Jordanian families of Arab descent. CONCLUSIONS: The present findings can be used in estimation of prevalence of peg-shaped teeth in the Jordanian population. However, our findings revealed that there is no evidence that the MSX1 polymorphisms had a crucial role in the peg-shaped teeth phenomenon, emphasizing that other genes might have this role. These findings are beneficial for clinicians to comprehensively understand the molecular aspects of teeth abnormalities.

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.

Association of DRD4 exon III and 5-HTTLPR VNTR genetic polymorphisms with psychiatric symptoms in hemodialysis patients.

Mental illness is prevalent among hemodialysis (HD) patients. Given that the dopaminergic and serotonergic pathways are involved in the etiology of psychiatric disease, this study evaluated the genetic association of dopamine D4 receptor (DRD4) and serotonin transporter (SLC6A4) genes with psychiatric symptom susceptibility among HD patients. Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depressive symptoms among patients (n = 265). Genetic polymorphisms of DRD4 (48 bp VNTR) and SLC6A4 (5-HTTLPR VNTR and rs25531) were examined using a conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, as appropriate. Significant differences were observed in the distribution of 5-HTTLPR genotypes, SLC6A4 tri-allelic-phased genotype, and DRD4-Exon III VNTR genotypes/alleles between patients with anxiety symptoms versus those with normal/borderline conditions (p<0.05). Binary logistic regression analyses showed that the heterozygous 4,5 VNTR genotype of DRD4 was associated with a higher risk of anxiety symptoms after adjusting for other covariates (odds ratio = 4.25, p = 0.028). None of the studied polymorphisms was linked to depression in HD patients. Collectively, the current findings provide genetic clues to psychopathology in HD patients and suggest that the DRD4 exon III VNTR polymorphism is involved in the etiology of anxiety in this patient population.

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.

Family-based association study of genetic analysis of paired box gene 9 polymorphisms in the peg-shaped teeth in the Jordanian Arab population.

OBJECTIVE: The aim of this study is to genotype thirteen Single Nucleotide Polymorphisms (SNPs) within the paired box gene 9 (PAX9) in 36 Jordanian Arab families with peg-shaped teeth, and also to investigate the association between the PAX9 gene and peg-shaped teeth disorder. METHODS: Genomic DNA samples were extracted from families according to distinguished processes. Then, DNA was amplified by polymerase chain reaction technique (PCR) using specified primers for the exons of the PAX9 gene. In addition, single nucleotide polymorphisms analysis was conducted using the DNA sequencing genotyping method to identify specific single nucleotide polymorphisms in the PAX9 gene associated with peg-shaped teeth. RESULTS: Thirteen single nucleotide polymorphisms in the PAX9 gene (Chromosome 14q13.3) were used; seven of them (rs104894467, rs104894469, rs28933373, rs28933970, rs28933971, rs28933972, and rs7143727) were non-polymorphic, and the other six were polymorphic (rs2073244, rs2073246, rs2295222, rs4904155, rs4904210, and rs12881240). Both rs12881240 and rs2295222 SNPs showed significant association with peg-shaped teeth disorder (P < 0.05). Moreover, the haplotype genetic analysis revealed that there is a genetic association with peg-shaped teeth disorder susceptibility (P < 0.05) in the Jordanian families of Arab descent. CONCLUSION: Our findings exhibited significant variations compared to the data recorded from other countries.

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.

The Associations of Common Genetic Susceptibility Variants with Breast Cancer in Jordanian Arabs: A Case-Control Study.

OBJECTIVE: In Jordan, breast cancer (BC) affects a substantial proportion of Jordanian women, highlighting the need for studies to be carried out regarding the genetic component of the disease. The aim of the present study was to investigate the interaction between BC risk and prognosis and polymorphisms in genes (ATM, CASP8, FGFR2, FN1, IGF1, LSP1, MAP3K, MMP7, and RHOC) that were chosen for this study previously reported as having a role in the disease. MATERIALS AND METHODS: Blood samples were collected from 242 BC patients and 231 disease-free volunteers recruited from the Jordanian population. DNA was extracted from blood and each sample was sent to the Australian Genome Research Facility for genotyping. RESULTS: The rs1219648 SNP of the FGFR2 gene was the only investigated variant to show any direct association with BC in Jordanian women (p-value = 0.04). However, the CASP8rs6760993 SNP was found to be significantly associated with BC (p-value = 0.04) when using the dominant model. Other gene polymorphisms showed varying levels of association between some investigated SNPs and different BC risk and prognostic factors. CONCLUSION: Despite reports to the contrary in other populations, most of the investigated genes and their respective SNPs did not show any significant association with BC in Jordanian women. Our results underline the need for independent BC research to be carried out in the Jordanian population to decipher the genetic basis of the disease.
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The difference in knowledge and concerns between healthcare professionals and patients about genetic-related issues: A questionnaire-based study.

Effective adoption of genetics in clinical practice requires the support of and interaction between the different partners of healthcare system; healthcare professionals (HCPs) and patients. The study aimed to assess and compare the knowledge, factors affecting the knowledge, and concerns of HCPs and patients regarding genetic-related issues such as lack of knowledge about genetics and genetic conditions, awareness of the importance of genetics in clinical practice and genetic services and resources deficits. A cross sectional study was conducted in different areas of Jordan using a convenient sampling approach. An English questionnaire was self-administered to HCPs. Face-to-face interviews were conducted with patients in Arabic by trained researcher. A total of 1000 HCPs and 1448 patients were recruited. There was a significant difference (p<0.001) in the knowledge between HCPs and patients. Among HCPs, physicians (OR = 2.278, 95%CI = 1.410-3.680, p = 0.001) and pharmacists (OR = 2.163, 95%CI = 1.362-3.436, p = 0.001) were more knowledgeable than nurses. In addition, females were more knowledgeable than males (OR = 1.717, 95%CI = 1.203-2.451, p = 0.003). Among patients, participants who had a bachelor degree (OR = 1.579, 95%CI = 1.231-2.025, p<0.001) were more knowledgeable compared to those who only had school education. HCPs appeared to have more concerns than patients (p<0.001) regarding all genetic-related issues. These findings suggested a positive association between education and genetic knowledge as well as concerns; as HCPs were more knowledgeable and concerned than patients. Appropriate integration and expansion of basic genetic knowledge courses and clinical genetic training in the curriculum should be adopted to prepare HCPs to enhance the integration of genetic information in clinical settings.

Genetic Association of SH2B1 Gene Polymorphisms in Jordanian Arab Patients with Type 2 Diabetes Mellitus.

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. The normality of the data distribution was statically analysed by the Shapiro-Wilk test with a P-value >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 (χ 2 test, P < 0.001). Additionally, rs143212778 SNP presented a genetic correlation with T2DM patients (χ 2 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.

WITHDRAWN: Evaluation of the factors that may contribute to the responsiveness of anti-epileptic treatments in pediatric patients, a study from Jordan.

This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the publication of this paper, which had been rejected by the editor. This error bears no reflection on the editor. The publisher apologizes to the authors, editor and the readers for this unfortunate error. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Genetic Analysis Of ABCA1 Gene Of Primary Glaucoma In Jordanian Arab Population.

BACKGROUND: Glaucoma is a neurodegenerative disease that leads to progressive loss of retinal ganglion cells, causing irreversible visual field defects. At the present time, glaucoma is clinically defined but the exact etiology is unknown. The aim of this study is to genotype rs2472493 and rs2487032 SNIPs within ABCA1 gene in 52 Jordanian Arab patients with primary glaucoma and 96 control subjects, and also to investigate the genetic association of these SNPs with primary glaucoma. METHODS: DNA was extracted from both patients and controls according to a well-established procedure. Then, DNA was amplified by PCR using specific primers for this gene. Analysis of polymorphisms was carried out by using DNA sequencing genotyping method. RESULTS: The results showed that the two SNPs (rs2472493 and rs2487032) located upstream of ABCA1 gene have no significant associations with primary glaucoma disorder (P > 0.05). CONCLUSION: This study is the first of its kind to reveal no genetic association between ABCA1 gene and primary glaucoma disorder in Jordanian population of Arab descent.

Investigating the Contribution of NPSR1, IL-6 and BDNF Polymorphisms to Depressive and Anxiety Symptoms in Hemodialysis Patients.

AIMS: Psychological symptoms are prevalent in hemodialysis (HD) patients. Previous investigations showed that brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) as well as the interaction with neuropeptide S receptor 1 (NPSR1) are linked to the development of psychological distress. This study examined the association of polymorphisms of genes encoding these proteins with depression and anxiety in a representative group of Jordanian HD patients. METHODS: A total of 302 HD patients were involved in the study and categorized into three groups based on the Hospital Anxiety and Depression Scale, HADS-D or HADS-A scores as follows: normal (<7), mild (8-10) and moderate-severe (11-21). Single nucleotide polymorphism (SNP) of NPSR1 Asn107Ile (rs324981), IL-6 G174C (rs1800795), and BDNF Val66Met (rs6265) was genotyped using blood samples. RESULTS: The frequency of Ile-allele of NPSR1 Asn107Ile was significantly higher in patients with moderate-severe HADS-A scores versus normal (53% vs. 40.8%, p = .035). Using ordinal regression analysis, Asn-allele of NPSR1 polymorphism was nominally significantly associated with a lower risk of anxiety (OR = 0.57, CI: 0.33-0.97, p = .038) after adjusting for other covariates. A marginally significant difference in genotype distribution of IL-6 G174C was observed among patients according to HADS-D scores (p = .05). Furthermore, carriers of IL-6174 CC genotype showed lower median IL-6 serum concentration versus carriers of GG genotype (5.2 vs. 1.35 pg/mL, p < .05). CONCLUSIONS: The results support the genetic role of NPSR1 in the pathogenesis of anxiety and suggest that carriers of NPSR1 Ile-allele are at increased risk of anxiety in HD patients. Neither BDNF Val66Met nor IL-6 G174C were linked to psychological symptoms. Future studies among other ethnicities are necessary to verify the observations.