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Mary Jeanne Kreek - One of the best experts on this subject based on the ideXlab platform.
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Dopaminergic pathway polymorphisms and Heroin Addiction: further support for association of CSNK1E variants.
Pharmacogenomics, 2014Co-Authors: Orna Levran, Jurg Ott, Matthew Randesi, John Rotrosen, Miriam Adelson, Einat Peles, Joel Correa Da Rosa, Mary Jeanne KreekAbstract:Background & aim: The dopaminergic pathways have been implicated in the etiology of drug Addictions. The aim of this study was to determine if variants in dopaminergic genes are associated with Heroin Addiction. Materials & methods: The study includes 828 former Heroin addicts and 232 healthy controls, of predominantly European ancestry. Ninety seven SNPs (13 genes) were analyzed. Results: Nine nominally significant associations were observed at CSNK1E, ANKK1, DRD2 and DRD3. Conclusion: The results support our previous report of association of CSNK1E SNP rs1534891 with protection from Heroin Addiction. CSNK1E interacts with circadian rhythms and DARPP-32 and has been implicated in negative regulation of sensitivity to opioids in rodents. It may be a target for drug Addiction treatment.
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Genome-wide association study identifies genes that may contribute to risk for developing Heroin Addiction.
Psychiatric genetics, 2010Co-Authors: David A. Nielsen, Jurg Ott, Vadim Yuferov, Mary Jeanne KreekAbstract:OBJECTIVES We have used genome-wide association studies to identify variants that are associated with vulnerability to develop Heroin Addiction. METHODS DNA from 325 methadone stabilized, former severe Heroin addicts and 250 control individuals were pooled by ethnicity (Caucasian and African-American) and analyzed using the Affymetrix GeneChip Mapping 100 K Set. Genome-wide association tests were conducted. RESULTS The strongest association with vulnerability to develop Heroin Addiction, with experiment-wise significance (P=0.035), was found in Caucasians with the variant rs10494334, a variant in an unannotated region of the genome (1q23.3). In African Americans, the variant most significantly associated with the Heroin Addiction vulnerability was rs950302, found in the cytosolic dual specificity phosphatase 27 gene DUSP27 (point-wise P=0.0079). Furthermore, analysis of the top 500 variants with the most significant associations (point-wise P< or =0.0036) in Caucasians showed that three of these variants are clustered in the regulating synaptic membrane exocytosis protein 2 gene RIMS2. Of the top 500 variants in African-Americans (point-wise P< or =0.0238), three variants are in the cardiomyopathy associated 3 gene CMYA3. CONCLUSION This study identifies new genes and variants that may increase an individual's vulnerability to develop Heroin Addiction.
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Heroin Addiction in African Americans: a hypothesis-driven association study.
Genes brain and behavior, 2009Co-Authors: Orna Levran, Jurg Ott, Douglas Londono, Paul Casadonte, Shirley Linzy, Matthew Randesi, Kim O'hara, John Rotrosen, Miriam Adelson, Mary Jeanne KreekAbstract:Heroin Addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify gene variants associated with Heroin Addiction in African Americans. The emphasis was on genes involved in reward modulation, behavioral control, cognitive function, signal transduction and stress response. We have performed a case-control association analysis by screening with 1350 variants of 130 genes. The sample consisted of 202 former severe Heroin addicts in methadone treatment and 167 healthy controls with no history of drug abuse. Single nucleotide polymorphism (SNP), haplotype and multi-SNP genotype pattern analyses were performed. Seventeen SNPs showed point-wise significant association with Heroin Addiction (nominal P< 0.01). These SNPs are from genes encoding several receptors: adrenergic (ADRA1A), arginine vasopressin (AVPR1A), cholinergic (CHRM2), dopamine (DRD1), GABA-A (GABRB3), glutamate (GRIN2A) and serotonin (HTR3A) as well as alcohol dehydrogenase (ADH7), glutamic acid decarboxylase (GAD1 and GAD2), the nucleoside transporter (SLC29A1) and diazepam-binding inhibitor (DBI). The most significant result of the analyses was obtained for the GRIN2A haplotype G-A-T (rs4587976-rs1071502-rs1366076) with protective effect (P(uncorrected) = 9.6E- 05, P(corrected) = 0.058). This study corroborates several reported associations with alcohol and drug Addiction as well as other related disorders and extends the list of variants that may affect the development of Heroin Addiction. Further studies will be necessary to replicate these associations and to elucidate the roles of these variants in drug Addiction vulnerability.
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Genotype patterns that contribute to increased risk for or protection from developing Heroin Addiction.
Molecular psychiatry, 2008Co-Authors: David A. Nielsen, Jurg Ott, Vadim Yuferov, A Chen, Orna Levran, Mary Jeanne KreekAbstract:A genome-wide association study was conducted using microarray technology to identify genes that may be associated with the vulnerability to develop Heroin Addiction, using DNA from 104 individual former severe Heroin addicts (meeting Federal criteria for methadone maintenance) and 101 individual control subjects, all Caucasian. Using separate analyses for autosomal and X chromosomal variants, we found that the strongest associations of allele frequency with Heroin Addiction were with the autosomal variants rs965972, located in the Unigene cluster Hs.147755 (experiment-wise q=0.053), and rs1986513 (q=0.187). The three variants exhibiting the strongest association with Heroin Addiction by genotype frequency were rs1714984, located in an intron of the gene for the transcription factor myocardin (P=0.000022), rs965972 (P=0.000080) and rs1867898 (P=0.000284). One genotype pattern (AG-TT-GG) was found to be significantly associated with developing Heroin Addiction (odds ratio (OR)=6.25) and explained 27% of the population attributable risk for Heroin Addiction in this cohort. Another genotype pattern (GG-CT-GG) of these variants was found to be significantly associated with protection from developing Heroin Addiction (OR=0.13), and lacking this genotype pattern explained 83% of the population attributable risk for developing Heroin Addiction. Evidence was found for involvement of five genes in Heroin Addiction, the genes coding for the μ opioid receptor, the metabotropic receptors mGluR6 and mGluR8, nuclear receptor NR4A2 and cryptochrome 1 (photolyase-like). This approach has identified several new genes potentially associated with Heroin Addiction and has confirmed the role of OPRM1 in this disease.
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TPH2 and TPH1 : Association of Variants and Interactions with Heroin Addiction
Behavior genetics, 2008Co-Authors: David A. Nielsen, Sandra Barral, Dmitri Proudnikov, Scott Kellogg, Jurg Ott, Mary Jeanne KreekAbstract:The tryptophan hydroxylase 2 gene (TPH2) was resequenced at the 5′ upstream, coding, and 3′ downstream regions, including all 11 exons in 185 subjects. Twenty-three novel and 14 known variants were identified. In a cohort of 583 consecutively ascertained subjects, including normal volunteers and those with specific addictive diseases, six common TPH2 and one TPH1 variant were genotyped. Allele frequencies of three TPH2 variants and the TPH1 variant varied significantly among the four ethnic groups within the control subjects. Of these subjects, 385 who met Heroin Addiction or control criteria and were of Caucasian, African-American, or Hispanic ethnicity were examined for potential association with vulnerability to develop Heroin Addiction. At the two locus genotype level in Hispanics, the TPH1 rs1799913 variant was found to significantly interact with the TPH2 rs7963720 variant and Heroin Addiction (P = 0.022), and with the TPH2 rs4290270 variant and Heroin Addiction (P = 0.011). In the African-American group, a significant association of a specific TPH2 haplotype with Heroin Addiction also was found (SNPHAP, P = 0.004; PHASE P = 0.036).
Jianghua Lai - One of the best experts on this subject based on the ideXlab platform.
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A Population-Based Study of Four Genes Associated with Heroin Addiction in Han Chinese.
PloS one, 2016Co-Authors: Xiaomeng Qiao, Jianghua Lai, Fangyuan Yin, Hao Guo, Xin Huang, Shuguang WeiAbstract:Recent studies have shown that variants in FAT atypical cadherin 3 (FAT3), kinectin 1 (KTN1), discs large homolog2 (DLG2) and deleted in colorectal cancer (DCC) genes influence the structure of the human mesolimbic reward system. We conducted a systematic analysis of the potential functional single nucleotide polymorphisms (SNPs) in these genes associated with Heroin Addiction. We scanned the functional regions of these genes and identified 20 SNPs for genotyping by using the SNaPshot method. A total of 1080 samples, comprising 523 cases and 557 controls, were analyzed. We observed that DCC rs16956878, rs12607853, and rs2292043 were associated with Heroin Addiction. The T alleles of rs16956878 (p = 0.0004) and rs12607853 (p = 0.002) were significantly enriched in the case group compared with the controls. A lower incidence of the C allele of rs2292043 (p = 0.002) was observed in the case group. In block 2 of DCC (rs2292043-rs12607853-rs16956878), the frequency of the T-T-T haplotype was significantly higher in the case group than in the control group (p = 0.024), and fewer C-C-C haplotypes (p = 0.006) were detected in the case group. DCC may be an important candidate gene in Heroin Addiction, and rs16956878, rs12607853, and rs2292043 may be risk factors, thereby providing a basis for further genetic and biological research.
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Analysis of variations in the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene reveals their relative importance as genetic susceptibility factors for Heroin Addiction.
PloS one, 2013Co-Authors: Bin Zhao, Yongsheng Zhu, Wei Wang, Haimin Cui, Yunpeng Wang, Jianghua LaiAbstract:The glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor was recently shown to be involved in the development of opiate Addiction. Genetic polymorphisms in GRIN2A have a plausible role in modulating the risk of Heroin Addiction. An association of GRIN2A single-nucleotide polymorphisms (SNPs) with Heroin Addiction was found earlier in African Americans. To identify markers that contribute to the genetic susceptibility to Heroin Addiction, we examined the potential association between Heroin Addiction and forty polymorphisms of the GRIN2A gene using the MassARRAY system and GeneScan in this study. The frequency of the (GT)26 repeats (rs3219790) in the Heroin Addiction group was significantly higher than that in the control group (χ2 = 5.360, P = 0.021). The allele frequencies of three polymorphisms (rs1102972, rs1650420, and rs3104703 in intron 3) were strongly associated with Heroin Addiction (P
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analysis of variations in the glutamate receptor n methyl d aspartate 2a grin2a gene reveals their relative importance as genetic susceptibility factors for Heroin Addiction
PLOS ONE, 2013Co-Authors: Bin Zhao, Yongsheng Zhu, Wei Wang, Haimin Cui, Yunpeng Wang, Jianghua LaiAbstract:The glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor was recently shown to be involved in the development of opiate Addiction. Genetic polymorphisms in GRIN2A have a plausible role in modulating the risk of Heroin Addiction. An association of GRIN2A single-nucleotide polymorphisms (SNPs) with Heroin Addiction was found earlier in African Americans. To identify markers that contribute to the genetic susceptibility to Heroin Addiction, we examined the potential association between Heroin Addiction and forty polymorphisms of the GRIN2A gene using the MassARRAY system and GeneScan in this study. The frequency of the (GT)26 repeats (rs3219790) in the Heroin Addiction group was significantly higher than that in the control group (χ2 = 5.360, P = 0.021). The allele frequencies of three polymorphisms (rs1102972, rs1650420, and rs3104703 in intron 3) were strongly associated with Heroin Addiction (P<0.001, 0.0002, and <0.001, after Bonferroni correction). Three additional SNPs from the same intron (rs1071502, rs6497730, and rs1070487) had nominally significant P values for association (P<0.05), but did not pass the threshold value. Haplotype analysis revealed that the G-C-T-C-C-T-A (block 6) and T-T (block 10) haplotypes of the GRIN2A gene displayed a protective effect (P = <0.001 and 0.003). These findings point to a role for GRIN2A polymorphisms in Heroin Addiction among the Han Chinese from Shaanxi province, and may be informative for future genetic or neurobiological studies on Heroin Addiction.
Jurg Ott - One of the best experts on this subject based on the ideXlab platform.
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Dopaminergic pathway polymorphisms and Heroin Addiction: further support for association of CSNK1E variants.
Pharmacogenomics, 2014Co-Authors: Orna Levran, Jurg Ott, Matthew Randesi, John Rotrosen, Miriam Adelson, Einat Peles, Joel Correa Da Rosa, Mary Jeanne KreekAbstract:Background & aim: The dopaminergic pathways have been implicated in the etiology of drug Addictions. The aim of this study was to determine if variants in dopaminergic genes are associated with Heroin Addiction. Materials & methods: The study includes 828 former Heroin addicts and 232 healthy controls, of predominantly European ancestry. Ninety seven SNPs (13 genes) were analyzed. Results: Nine nominally significant associations were observed at CSNK1E, ANKK1, DRD2 and DRD3. Conclusion: The results support our previous report of association of CSNK1E SNP rs1534891 with protection from Heroin Addiction. CSNK1E interacts with circadian rhythms and DARPP-32 and has been implicated in negative regulation of sensitivity to opioids in rodents. It may be a target for drug Addiction treatment.
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Genome-wide association study identifies genes that may contribute to risk for developing Heroin Addiction.
Psychiatric genetics, 2010Co-Authors: David A. Nielsen, Jurg Ott, Vadim Yuferov, Mary Jeanne KreekAbstract:OBJECTIVES We have used genome-wide association studies to identify variants that are associated with vulnerability to develop Heroin Addiction. METHODS DNA from 325 methadone stabilized, former severe Heroin addicts and 250 control individuals were pooled by ethnicity (Caucasian and African-American) and analyzed using the Affymetrix GeneChip Mapping 100 K Set. Genome-wide association tests were conducted. RESULTS The strongest association with vulnerability to develop Heroin Addiction, with experiment-wise significance (P=0.035), was found in Caucasians with the variant rs10494334, a variant in an unannotated region of the genome (1q23.3). In African Americans, the variant most significantly associated with the Heroin Addiction vulnerability was rs950302, found in the cytosolic dual specificity phosphatase 27 gene DUSP27 (point-wise P=0.0079). Furthermore, analysis of the top 500 variants with the most significant associations (point-wise P< or =0.0036) in Caucasians showed that three of these variants are clustered in the regulating synaptic membrane exocytosis protein 2 gene RIMS2. Of the top 500 variants in African-Americans (point-wise P< or =0.0238), three variants are in the cardiomyopathy associated 3 gene CMYA3. CONCLUSION This study identifies new genes and variants that may increase an individual's vulnerability to develop Heroin Addiction.
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Heroin Addiction in African Americans: a hypothesis-driven association study.
Genes brain and behavior, 2009Co-Authors: Orna Levran, Jurg Ott, Douglas Londono, Paul Casadonte, Shirley Linzy, Matthew Randesi, Kim O'hara, John Rotrosen, Miriam Adelson, Mary Jeanne KreekAbstract:Heroin Addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify gene variants associated with Heroin Addiction in African Americans. The emphasis was on genes involved in reward modulation, behavioral control, cognitive function, signal transduction and stress response. We have performed a case-control association analysis by screening with 1350 variants of 130 genes. The sample consisted of 202 former severe Heroin addicts in methadone treatment and 167 healthy controls with no history of drug abuse. Single nucleotide polymorphism (SNP), haplotype and multi-SNP genotype pattern analyses were performed. Seventeen SNPs showed point-wise significant association with Heroin Addiction (nominal P< 0.01). These SNPs are from genes encoding several receptors: adrenergic (ADRA1A), arginine vasopressin (AVPR1A), cholinergic (CHRM2), dopamine (DRD1), GABA-A (GABRB3), glutamate (GRIN2A) and serotonin (HTR3A) as well as alcohol dehydrogenase (ADH7), glutamic acid decarboxylase (GAD1 and GAD2), the nucleoside transporter (SLC29A1) and diazepam-binding inhibitor (DBI). The most significant result of the analyses was obtained for the GRIN2A haplotype G-A-T (rs4587976-rs1071502-rs1366076) with protective effect (P(uncorrected) = 9.6E- 05, P(corrected) = 0.058). This study corroborates several reported associations with alcohol and drug Addiction as well as other related disorders and extends the list of variants that may affect the development of Heroin Addiction. Further studies will be necessary to replicate these associations and to elucidate the roles of these variants in drug Addiction vulnerability.
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genetic susceptibility to Heroin Addiction a candidate gene association study
Genes Brain and Behavior, 2008Co-Authors: Orna Levran, David A. Nielsen, Douglas Londono, K Ohara, E Peles, J Rotrosen, Paul Casadonte, Shirley Linzy, Matthew Randesi, Jurg OttAbstract:Heroin Addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop Heroin Addiction by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe Heroin addicts in methadone treatment, and 184 healthy controls with no history of drug abuse. Nine variants, in six genes, showed the lowest nominal P values in the association tests (P < 0.01). These variants were in noncoding regions of the genes encoding the mu (OPRM1; rs510769 and rs3778151), kappa (OPRK1; rs6473797) and delta (OPRD1; rs2236861, rs2236857 and rs3766951) opioid receptors; the neuropeptide galanin (GAL; rs694066); the serotonin receptor subtype 3B (HTR3B; rs3758987) and the casein kinase 1 isoform epsilon (CSNK1E; rs1534891). Several haplotypes and multilocus genotype patterns showed nominally significant associations (e.g. OPRM1; P = 0.0006 and CSNK1E; P = 0.0007). Analysis of a combined effect of OPRM1 and OPRD1 showed that rs510769 and rs2236861 increase the risk of Heroin Addiction (P = 0.0005). None of these associations remained significant after adjustment for multiple testing. This study suggests the involvement of several genes and variants in Heroin Addiction, which is worthy of future study.
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Genetic susceptibility to Heroin Addiction: a candidate gene association study
Genes brain and behavior, 2008Co-Authors: Orna Levran, David A. Nielsen, Douglas Londono, E Peles, J Rotrosen, Paul Casadonte, Shirley Linzy, Matthew Randesi, K. O’hara, Jurg OttAbstract:Heroin Addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop Heroin Addiction by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe Heroin addicts in methadone treatment, and 184 healthy controls with no history of drug abuse. Nine variants, in six genes, showed the lowest nominal P values in the association tests (P
Mark Adams - One of the best experts on this subject based on the ideXlab platform.
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Telltale Heroin Addiction Symptoms | WhiteSands Treatment
2018Co-Authors: Mark AdamsAbstract:How do you know someone is abusing Heroin? Discover the telltale Heroin Addiction signs. To get professional help today, call WhiteSands at (877) 855 3470.
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Heroin Addiction Treatment: How Long is Rehab?
2017Co-Authors: Mark AdamsAbstract:How long does Heroin Addiction treatment need to last for it to be effective? Discover how WhiteSands Treatment can help by calling 877-855-3470.
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The Reason Behind The Rise of Heroin Addiction | Opioid Epidemic Stats
2017Co-Authors: Mark AdamsAbstract:Heroin Addiction has become a serious public health concern across the country. FInd out what has lead to the rise in Addiction and where to find help.
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Fort Myers Heroin Rehab | Heroin Detox Fort Myers Heroin Addiction
2017Co-Authors: Mark AdamsAbstract:Do you feel stuck in the cycle of Heroin Addiction? Our Addiction specialists can help. Contact us by calling (877) 855-3470 today!
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Withdrawal Symptoms of Heroin | Heroin Addiction Symptoms
2017Co-Authors: Mark AdamsAbstract:If you're worried about someone having an Addiction, here is what you should know about Heroin Addiction and withdrawal symptoms of Heroin.
Wayne Hall - One of the best experts on this subject based on the ideXlab platform.
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Heroin Addiction: theory, research and treatment vol 3, Treatment advances and AIDS - Platt J.J.(book review)
Addiction, 1996Co-Authors: Wayne HallAbstract:In this book Platt updates an earlier review of research on the treatment of Heroin Addiction. He includes new material on the epidemiology of HIV and AIDS in injecting drug users and discusses various approaches to the prevention of its transmission. In doing so, Platt provides a useful and accessible introduction to the extensive literature that has developed on the pharmacological treatment of Heroin Addiction in the past 10 years.