Dataset Information

Custom genotyping for substance addiction susceptibility genes in Jordanians of Arab descent.

ABSTRACT: BACKGROUND: Both 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). RESULTS: This 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 (?2 (2, N?=?460)?=?21, p-value?=?0.000026) and 1.78 (?2 (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. CONCLUSION: This 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.

SUBMITTER: Al-Eitan LN

PROVIDER: S-EPMC3477049 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Custom genotyping for substance addiction susceptibility genes in Jordanians of Arab descent.

Al-Eitan Laith N LN Jaradat Saied A SA Hulse Gary K GK Tay Guan K GK

BMC research notes 20120910

<h4>Background</h4>Both 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. Patien ...[more]

PMID: 22963930

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Project description:Addictive disorders are a class of chronic, relapsing mental disorders that are responsible for increased risk of mental and medical disorders and represent the largest, potentially modifiable cause of death. Tobacco dependence is associated with increased risk of disease and premature death. While tobacco control efforts and therapeutic interventions have made good progress in reducing smoking prevalence, challenges remain in optimizing their effectiveness based on patient characteristics, including genetic variation. In order to maximize collaborative efforts to advance addiction research, we have developed a genotyping array called Smokescreen. This custom array builds upon previous work in the analyses of human genetic variation, the genetics of addiction, drug metabolism, and response to therapy, with an emphasis on smoking and nicotine addiction.The Smokescreen genotyping array includes 646,247 markers in 23 categories. The array design covers genome-wide common variation (65.67, 82.37, and 90.72% in African (YRI), East Asian (ASN), and European (EUR) respectively); most of the variation with a minor allele frequency ? 0.01 in 1014 addiction genes (85.16, 89.51, and 90.49% for YRI, ASN, and EUR respectively); and nearly all variation from the 1000 Genomes Project Phase 1, NHLBI GO Exome Sequencing Project and HapMap databases in the regions related to smoking behavior and nicotine metabolism: CHRNA5-CHRNA3-CHRNB4 and CYP2A6-CYP2B6. Of the 636 pilot DNA samples derived from blood or cell line biospecimens that were genotyped on the array, 622 (97.80%) passed quality control. In passing samples, 90.08% of markers passed quality control. The genotype reproducibility in 25 replicate pairs was 99.94%. For 137 samples that overlapped with HapMap2 release 24, the genotype concordance was 99.76%. In a genome-wide association analysis of the nicotine metabolite ratio in 315 individuals participating in nicotine metabolism laboratory studies, we identified genome-wide significant variants in the CYP2A6 region (min p = 9.10E-15).We developed a comprehensive genotyping array for addiction research and demonstrated its analytic validity and utility through pilot genotyping of HapMap and study samples. This array allows researchers to perform genome-wide, candidate gene, and pathway-based association analyses of addiction, tobacco-use, treatment response, comorbidities, and associated diseases in a standardized, high-throughput platform.

Project description:BackgroundSubstance use disorders, which include substance abuse and substance dependence, are present in all regions of the world including Middle Eastern Arab countries. Bibliometric analysis is an increasingly used tool for research assessment. The main objective of this study was to assess research productivity in the field of substance use disorders in Arab countries using bibliometric indicators.MethodologyOriginal or review research articles authored or co-authored by investigators from Arab countries about substance use disorders during the period 1900-2013 were retrieved using the ISI Web of Science database. Research activity was assessed by analyzing the annual research productivity, contribution of each Arab country, names of journals, citations, and types of abused substances.ResultsFour hundred and thirteen documents in substance use disorders were retrieved. Annual research productivity was low but showed a significant increase in the last few years. In terms of quantity, Kingdom of Saudi Arabia (83 documents) ranked first in research about substance use disorders while Lebanon (17.4 documents per million) ranked first in terms of number of documents published per million inhabitants. Retrieved documents were found in different journal titles and categories, mostly in Drug and Alcohol Dependence Journal. Authors from USA appeared in 117 documents published by investigators from Arab countries. Citation analysis of retrieved documents showed that the average citation per document was 10.76 and the h - index was 35. The majority of retrieved documents were about tobacco and smoking (175 documents) field while alcohol consumption and abuse research was the least with 69 documents.ConclusionThe results obtained suggest that research in this field was largely neglected in the past. However, recent research interest was observed. Research output on tobacco and smoking was relatively high compared to other substances of abuse like illicit drugs and medicinal agents. Governmental funding for academics and mental health graduate programs to do research in the field of substance use disorders is highly recommended.

Dataset Information

Custom genotyping for substance addiction susceptibility genes in Jordanians of Arab descent.

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Custom genotyping for substance addiction susceptibility genes in Jordanians of Arab descent.

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