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

<p>Abstract</p> <p>Background</p> <p>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 (<it>n</it> = 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 (<it>DRD1</it>, <it>DRD2</it>, <it>DRD3</it>, <it>DRD4</it>, <it>DRD5</it>, <it>BDNF</it>, <it>SLC6A3</it> and <it>COMT</it>).</p> <p>Results</p> <p>This study revealed six new associations involving SNPs within <it>DRD2</it> gene on chromosome 11. These six SNPs within the <it>DRD2</it> 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 <it>DRD2</it>, with the overall estimate of effects returning an odds ratio of 3.37 (<it>χ2</it> (2, <it>N</it> = 460) = 21, <it>p-value</it> = 0.000026) and 1.78 (<it>χ2</it> (2, <it>N</it> = 460) = 8, <it>p-value</it> = 0.001), respectively. It has been suggested that <it>DRD2</it>, dopamine receptor D2, plays an important role in dopamine secretion and the signal pathways of dopaminergic reward and drug addiction.</p> <p>Conclusion</p> <p>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.</p

Genetic polymorphisms and personality in healthy adults: a systematic review and meta-analysis.

A meta-analysis was conducted on studies reporting data on associations between candidate genes and human personality. Studies reporting data for psychiatric populations (including organic disease and substance abuse) were excluded. A total of 46 studies contributed to the analysis. Pooled data using a fixed-effects model suggested significant associations between the 5HTT LPR, DRD4 c>t, DRD4 length, DRD2 A1/A2, DRD3 A1/A2 polymorphisms and personality traits. A multivariate analysis using a mixed-effects model and including age, sex and predominant ethnicity as covariates was applied to the analyses of 5HTT LPR and DRD4 length polymorphism data. Only the association between the 5HTT LPR polymorphism and avoidance traits remained significant (P=0.038). However, sensitivity analyses excluding data from studies reporting allele frequencies not in Hardy-Weinberg equilibrium and unpublished data resulted in this association no longer being significant. Implications for the design of future association studies of human personality are discussed, including the likely sample sizes that will be required to achieve sufficient power and the potential role of moderating variables such as sex