BackgroundBoth environmental and genetic factors contribute to individual susceptibility to initiation of substance use and vulnerability to addiction. Determining genetic risk factors can make an important contribution to understanding the processes leading to addiction. In order to identify gene(s) and mechanisms associated with substance addiction, a custom platform array search for a genetic association in a case/control of homogenous Jordanian Arab population was undertaken. Patients meeting the DSM-VI criteria for substance dependence (n = 220) and entering eight week treatment program at two Jordanian Drug Rehabilitation Centres were genotyped. In addition, 240 healthy controls were also genotyped. The sequenom MassARRAY system (iPLEX GOLD) was used to genotype 49 single nucleotide polymorphisms (SNPs) within 8 genes (DRD1, DRD2, DRD3, DRD4, DRD5, BDNF, SLC6A3 and COMT).ResultsThis study revealed six new associations involving SNPs within DRD2 gene on chromosome 11. These six SNPs within the DRD2 were found to be most strongly associated with substance addiction in the Jordanian Arabic sample. The strongest statistical evidence for these new association signals were from rs1799732 in the C/−C promoter and rs1125394 in A/G intron 1 regions of DRD2, with the overall estimate of effects returning an odds ratio of 3.37 (χ2 (2, N = 460) = 21, p-value = 0.000026) and 1.78 (χ2 (2, N = 460) = 8, p-value = 0.001), respectively. It has been suggested that DRD2, dopamine receptor D2, plays an important role in dopamine secretion and the signal pathways of dopaminergic reward and drug addiction.ConclusionThis study is the first to show a genetic link to substance addiction in a Jordanian population of Arab descent. These findings may contribute to our understanding of drug addiction mechanisms in Middle Eastern populations and how to manage or dictate therapy for individuals. Comparative analysis with different ethnic groups could assist further improving our understanding of these mechanisms.
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.
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.
Background Because of their broad applications in our life, nanoparticles are expected to be present in the environment raising many concerns about their possible adverse effects on the ecosystem of plants. The aim of this study was to examine the effect of different sizes and concentrations of iron oxide nanoparticles [(Fe 3 O 4 ) NPs] on morphological, physiological, biochemical, and ultrastructural parameters in tobacco ( Nicotiana tabacum var.2 Turkish). Results Lengths of shoots and roots of 5 nm-treated plants were significantly decreased in all nanoparticle-treated plants compared to control plants or plants treated with any concentration of 10 or 20 nm nanoparticles. The photosynthetic rate and leaf area were drastically reduced in 5 nm (Fe 3 O 4 ) NP-treated plants of all concentrations compared to control plants and plants treated with 10 or 20 nm (Fe 3 O 4 ) NPs. Accumulation of sugars in leaves showed no significant differences between the control plants and plants treated with iron oxide of all sizes and concentrations. In contrast, protein accumulation in plants treated with 5 nm iron oxide dramatically increased compared to control plants. Moreover, light and transmission electron micrographs of roots and leaves revealed that roots and chloroplasts of 5 nm (Fe 3 O 4 ) NPs-treated plants of all concentrations were drastically affected. Conclusions The size and concentration of nanoparticles are key factors affecting plant growth and development. The results of this study demonstrated that the toxicity of (Fe 3 O 4 ) NPs was clearly influenced by size and concentration. Further investigations are needed to elucidate more about NP toxicity in plants, especially at the molecular level. Electronic supplementary material The online version of this article (10.1186/s12870-019-1864-1) contains supplementary material, which is available to authorized users.
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