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David A Collier - One of the best experts on this subject based on the ideXlab platform.
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Allelic association analysis of the dopamine D2, D3, 5‐HT2A, and GABAAγ2 receptors and serotonin transporter genes with Heroin Abuse in Chinese subjects
American Journal of Medical Genetics, 2002Co-Authors: Tao Li, Xiehe Liu, El Wui Loh, David Ball, Jinghua Zhao, Pak C. Sham, Xun Hu, David A CollierAbstract:Five candidate genes, the receptors DRD2, DRD3, HTR2A and GABA(A)gamma2, and the serotonin transporter (5-HTT) were analyzed for association with Heroin Abuse. We examined three polymorphisms (promoter - 141DeltaC, Ser311Cys, and TaqI) in the DRD2 gene, one polymorphism (Ser9Gly) in the DRD3 gene, two polymorphisms (promoter - 1438G/A and T102C) in the HTR2A gene, two polymorphisms (VNTR and Del/Ins) in 5-HTT gene, and one polymorphism (G3145A) in GABA(A)gamma2 gene in 121 Chinese Heroin addicts and 194 controls. None of the polymorphisms differed significantly for allele, genotype, or haplotype frequencies, except for the DRD2 promoter polymorphism - 141DeltaC (genotype-wise and allele-wise, P = 0.05, uncorrected). An additional 344 subjects with Heroin Abuse and 104 controls were investigated for the - 141DeltaC polymorphism. In the second sample, there were no significant difference of genotype or allele frequencies between subjects with Heroin Abuse and normal controls. When we divided the sample by route of administration into nasal inhalers and IM or IV injectors, however, it produced a significant difference between inhalers of Heroin and controls (genotype-wise, P = 0.006, allele-wise, P = 0.016) but not for injectors of Heroin (genotype-wise, P = 0.81, allele-wise, P = 0.69). We also found that LD between all polymorphisms we examined in the gene was weak, possibly explaining why we see association of this polymorphism with Heroin Abuse but not with other markers in the gene. Overall our results indicates that the HTR2A, 5-HTT, DRD3 and GABA(A)gamma2 genes are not likely to be a major genetic risk factor for Heroin Abuse in this population, with the exception of possible association between nasal inhalation and DRD2 promoter - 141DeltaC polymorphism.
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Association analysis of polymorphisms in the DRD4 gene and Heroin Abuse in Chinese subjects
American Journal of Medical Genetics, 2000Co-Authors: Tao Li, Xiehe Liu, Zuo-hong Zhu, Jinghua Zhao, Pak C. Sham, Xun Hu, David A CollierAbstract:Heroin Abuse is a major social and public health problem in many parts of the world, yet relatively little is known about its etiology. Although genes play a role in determining susceptibility, they are expected to be of small effect with considerable heterogeneity. Because the dopamine system is involved in reward, its neurotransmitter receptors are candidates for etiological involvement in addiction. In the present study, we examine two polymorphisms in the dopamine D4 receptor, a VNTR in exon III and a point mutation in the promoter (-512C/T) that affects transcriptional efficiency. We examined a sample of 405 Heroin-abusing subjects and 304 controls from Sichuan Province, Southwest China. One hundred twenty-one of these cases and 154 controls were previously used in a study of the DRD4 VNTR [Li et al., 1997: Mol Psychiatry 2:413-416], and the remainder are newly ascertained. The two polymorphisms were in weak but detectable linkage disequilibrium (1,418 chromosomes, P < 0.00001, D' = 0.17). When we compared the Heroin-Abuse group with controls, we found no significant difference between the patients and controls for either polymorphism in the DRD4 gene or their haplotypes. We were also unable to replicate our earlier association between long DRD4 alleles and Heroin Abuse. However, division of the sample by route of administration (nasal inhalers or injectors) produced a significant difference between inhalers and controls for the DRD4 VNTR (six-fold corrected P = 0.018 by allele) but not for injectors of Heroin. The association we observed between inhalers and the DRD4 polymorphism is difficult to interpret, although it is possible that the association is explained by different levels of novelty seeking between the two subgroups.
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No association between (AAT)n repeats in the cannabinoid receptor gene (CNR1) and Heroin Abuse in a Chinese population.
Molecular psychiatry, 2000Co-Authors: Xiehe Liu, David Ball, Jinghua Zhao, Z H Zhu, P. C. Sham, David A CollierAbstract:No association between (AAT) n repeats in the cannabinoid receptor gene (CNR1) and Heroin Abuse in a Chinese population
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association analysis of polymorphisms in the mu opioid gene and Heroin Abuse in chinese subjects
Addiction Biology, 2000Co-Authors: Xiehe Liu, Zuo-hong Zhu, Jinghua Zhao, Pak C. Sham, David A CollierAbstract:We examined four polymorphisms in the mu opioid receptor gene in 282 Chinese Heroin addicts from Sichuan Province, Southwest China and compared the allele and genotype frequencies to those in 258 normal controls from the same geographic region. Two of these polymorphisms (Ala6Val and Ser147Cys) were not polymorphic in the Chinese, with only Ala6 and Ser147 observed. The frequencies of the two other polymorphisms were significantly different from those observed in Caucasians, African Americans and Native Americans. The Asn40Asp and IVS2 + 691G/C polymorphisms did not differ significantly for allele (p= 0.16; p = 0.21), genotype (p= 0.32; p = 0.09) or haplotype frequencies (p= 0.24) between the Chinese Heroin-addicted cases and normal controls. Similarly, we did not detect any association when the population was stratified by gender, route of administration (nasal inhalation and/or injection) and age-at-onset (above or below 25 years). This indicates that the mu opioid receptor is not likely to be a major genetic risk factor for Heroin Abuse in this population.
Narinder Pal Singh - One of the best experts on this subject based on the ideXlab platform.
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unusual complications of Heroin Abuse transverse myelitis rhabdomyolysis compartment syndrome and arf
Clinical Toxicology, 2008Co-Authors: Vaibhav Sahni, Dheeraj Garg, Sandeep Garg, S K Agarwal, Narinder Pal SinghAbstract:Introduction. Heroin overdose can cause various rare neurological complications like spongiform leukoencephalopathy, seizures, stroke, toxic amblyopia, transverse myelopathy, mononeuropathy, plexopathy, acute inflammatory demyelinating polyradiculoneuropathy, rhabdomyolysis, compartment syndrome, fibrosing myopathy, and acute bacterial myopathy. We report here the simultaneous presentation of multiple complications of Heroin toxicity. Case report. A young Heroin addict was found unarousable lying in the lotus posture. Examination showed quadriplegia and left leg gangrene. He subsequently developed Heroin-induced transverse myelitis, rhabdomyolysis, left leg compartment syndrome, and myoglobin-induced acute renal failure. Discussion. This case leads us to consider a common linked or systemic mechanism of injury rather than a local mechanism when multiple simultaneous organ failure occurs complicating Heroin Abuse.
Yasmin L. Hurd - One of the best experts on this subject based on the ideXlab platform.
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Heroin Abuse exaggerates age related deposition of hyperphosphorylated tau and p62 positive inclusions
Neurobiology of Aging, 2015Co-Authors: Monika Horvath, Yasmin L. Hurd, Gabor G Kovacs, Katalin Majtenyi, Mirjam I Lutz, Eva KellerAbstract:The observation of increased hyperphosphorylated tau levels correlating with microglial activation in opiate Abusers has been interpreted as predisposition to accelerated Alzheimer disease-related changes. The present study focused on evaluating additional neurodegeneration-related proteins, including α-synuclein and TDP-43, and p62-positive deposits. We performed a systematic mapping of protein deposits in the brains of 27 individuals with documented Heroin addiction (age: 19-40 years) and compared with 11 controls (age: 15-40 years). We confirm previous findings that Heroin addiction associates with tau hyperphosphorylation in predilection brain areas for aging and Alzheimer disease. Furthermore, we show that this occurs also in areas implicated in the molecular disturbances and in vivo neuronal networks related to Heroin Abuse. There was, however, no presence of amyloid-beta deposits. We extend previous findings by showing the lack of TDP-43 or α-synuclein pathology and emphasize the independent effect of the duration of drug use on the appearance of age-related p62-positive neuritic profiles. These observations provide unique insights about neuropathological alterations in the brains of young Heroin addicts and have implications about brain aging and the influences of environmental and toxic factors.
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Opioid neuropeptide genotypes in relation to Heroin Abuse: Dopamine tone contributes to reversed mesolimbic proenkephalin expression
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Andrej Nikoshkov, Katarina Drakenberg, Xinyu Wang, Monika Horvath, Eva Keller, Yasmin L. HurdAbstract:Striatal enkephalin and dynorphin opioid systems mediate reward and negative affect, respectively, relevant to addiction disorders. We examined polymorphisms of proenkephalin (PENK) and prodynorphin (PDYN) genes in relation to Heroin Abuse and gene expression in the human striatum and the relevance of genetic dopaminergic tone, critical for drug reward and striatal function. Heroin Abuse was significantly associated with PENK polymorphic 3′ UTR dinucleotide (CA) repeats; 79% of subjects homozygous for the 79-bp allele were Heroin Abusers. Such individuals tended to express higher PENK mRNA than the 81-bp homozygotes, but PENK levels within the nucleus accumbens (NAc) shell were most strongly correlated to catecholamine-O-methyltransferase (COMT) genotype. Control Met/Met individuals expressed lower PENK mRNA than Val carriers, a pattern reversed in Heroin users. Up-regulation of NAc PENK in Met/Met Heroin Abusers was accompanied by impaired tyrosine hydroxylase (TH) mRNA expression in mesolimbic dopamine neurons. In contrast to PENK, no association was detected between PDYN genotype (68-bp repeat element containing one to four copies of AP-1 binding sites in the promoter region) and Heroin Abuse, although there was a clear functional association with striatal PDYN mRNA expression: an increased number of inducible repeats (three and four) correlated with higher PDYN levels than adult or fetal subjects with noninducible (one and two) alleles. Moreover, PDYN expression was not related to COMT genotype. Altogether, the data suggest that dysfunction of the opioid reward system is significantly linked to opiate Abuse vulnerability and that Heroin use alters the apparent influence of heritable dopamine tone on mesolimbic PENK and TH function.
Xiehe Liu - One of the best experts on this subject based on the ideXlab platform.
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Allelic association analysis of the dopamine D2, D3, 5‐HT2A, and GABAAγ2 receptors and serotonin transporter genes with Heroin Abuse in Chinese subjects
American Journal of Medical Genetics, 2002Co-Authors: Tao Li, Xiehe Liu, El Wui Loh, David Ball, Jinghua Zhao, Pak C. Sham, Xun Hu, David A CollierAbstract:Five candidate genes, the receptors DRD2, DRD3, HTR2A and GABA(A)gamma2, and the serotonin transporter (5-HTT) were analyzed for association with Heroin Abuse. We examined three polymorphisms (promoter - 141DeltaC, Ser311Cys, and TaqI) in the DRD2 gene, one polymorphism (Ser9Gly) in the DRD3 gene, two polymorphisms (promoter - 1438G/A and T102C) in the HTR2A gene, two polymorphisms (VNTR and Del/Ins) in 5-HTT gene, and one polymorphism (G3145A) in GABA(A)gamma2 gene in 121 Chinese Heroin addicts and 194 controls. None of the polymorphisms differed significantly for allele, genotype, or haplotype frequencies, except for the DRD2 promoter polymorphism - 141DeltaC (genotype-wise and allele-wise, P = 0.05, uncorrected). An additional 344 subjects with Heroin Abuse and 104 controls were investigated for the - 141DeltaC polymorphism. In the second sample, there were no significant difference of genotype or allele frequencies between subjects with Heroin Abuse and normal controls. When we divided the sample by route of administration into nasal inhalers and IM or IV injectors, however, it produced a significant difference between inhalers of Heroin and controls (genotype-wise, P = 0.006, allele-wise, P = 0.016) but not for injectors of Heroin (genotype-wise, P = 0.81, allele-wise, P = 0.69). We also found that LD between all polymorphisms we examined in the gene was weak, possibly explaining why we see association of this polymorphism with Heroin Abuse but not with other markers in the gene. Overall our results indicates that the HTR2A, 5-HTT, DRD3 and GABA(A)gamma2 genes are not likely to be a major genetic risk factor for Heroin Abuse in this population, with the exception of possible association between nasal inhalation and DRD2 promoter - 141DeltaC polymorphism.
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Association analysis of polymorphisms in the DRD4 gene and Heroin Abuse in Chinese subjects
American Journal of Medical Genetics, 2000Co-Authors: Tao Li, Xiehe Liu, Zuo-hong Zhu, Jinghua Zhao, Pak C. Sham, Xun Hu, David A CollierAbstract:Heroin Abuse is a major social and public health problem in many parts of the world, yet relatively little is known about its etiology. Although genes play a role in determining susceptibility, they are expected to be of small effect with considerable heterogeneity. Because the dopamine system is involved in reward, its neurotransmitter receptors are candidates for etiological involvement in addiction. In the present study, we examine two polymorphisms in the dopamine D4 receptor, a VNTR in exon III and a point mutation in the promoter (-512C/T) that affects transcriptional efficiency. We examined a sample of 405 Heroin-abusing subjects and 304 controls from Sichuan Province, Southwest China. One hundred twenty-one of these cases and 154 controls were previously used in a study of the DRD4 VNTR [Li et al., 1997: Mol Psychiatry 2:413-416], and the remainder are newly ascertained. The two polymorphisms were in weak but detectable linkage disequilibrium (1,418 chromosomes, P < 0.00001, D' = 0.17). When we compared the Heroin-Abuse group with controls, we found no significant difference between the patients and controls for either polymorphism in the DRD4 gene or their haplotypes. We were also unable to replicate our earlier association between long DRD4 alleles and Heroin Abuse. However, division of the sample by route of administration (nasal inhalers or injectors) produced a significant difference between inhalers and controls for the DRD4 VNTR (six-fold corrected P = 0.018 by allele) but not for injectors of Heroin. The association we observed between inhalers and the DRD4 polymorphism is difficult to interpret, although it is possible that the association is explained by different levels of novelty seeking between the two subgroups.
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No association between (AAT)n repeats in the cannabinoid receptor gene (CNR1) and Heroin Abuse in a Chinese population.
Molecular psychiatry, 2000Co-Authors: Xiehe Liu, David Ball, Jinghua Zhao, Z H Zhu, P. C. Sham, David A CollierAbstract:No association between (AAT) n repeats in the cannabinoid receptor gene (CNR1) and Heroin Abuse in a Chinese population
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association analysis of polymorphisms in the mu opioid gene and Heroin Abuse in chinese subjects
Addiction Biology, 2000Co-Authors: Xiehe Liu, Zuo-hong Zhu, Jinghua Zhao, Pak C. Sham, David A CollierAbstract:We examined four polymorphisms in the mu opioid receptor gene in 282 Chinese Heroin addicts from Sichuan Province, Southwest China and compared the allele and genotype frequencies to those in 258 normal controls from the same geographic region. Two of these polymorphisms (Ala6Val and Ser147Cys) were not polymorphic in the Chinese, with only Ala6 and Ser147 observed. The frequencies of the two other polymorphisms were significantly different from those observed in Caucasians, African Americans and Native Americans. The Asn40Asp and IVS2 + 691G/C polymorphisms did not differ significantly for allele (p= 0.16; p = 0.21), genotype (p= 0.32; p = 0.09) or haplotype frequencies (p= 0.24) between the Chinese Heroin-addicted cases and normal controls. Similarly, we did not detect any association when the population was stratified by gender, route of administration (nasal inhalation and/or injection) and age-at-onset (above or below 25 years). This indicates that the mu opioid receptor is not likely to be a major genetic risk factor for Heroin Abuse in this population.
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Association analysis of the dopamine D4 gene exon III VNTR and Heroin Abuse in Chinese subjects.
Molecular Psychiatry, 1997Co-Authors: Hong-wen Deng, Xiehe Liu, Jinghua Zhao, Guiqing Cai, J Liu, R Wang, X Xiang, Robin M. MurrayAbstract:Although social and cultural influences are clearly important, family, twin and adoption studies indicate that genes contribute significantly to substance Abuse. Substance Abuse is associated with novelty seeking, a heritable human personality trait which may be influenced by alleles of the dopamine D4 (DRD4) gene exon III VNTR. Consequently Kotler et al analysed the DRD4 VNTR in opiate-dependent subjects from Israel, and found a significant excess of the 7-repeat allele. We have attempted to replicate this finding using a Han Chinese case-control sample of 121 Heroin-dependent subjects and 154 normal controls. We found two 7-repeat alleles which occurred exclusively in the patient group, and overall there was an excess of longer alleles, which did not reach significance (chi 2 = 7.04; P = 0.07). When the D4 VNTR was divided into 'long' (5-7 repeats) and 'short' (2-4 repeats), a significant excess of long alleles was observed in the patient group (P = 0.023, one-tailed), with an odds ratio of 2.30 (95% CI 1.07-4.93). We conclude that our findings support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for Heroin Abuse.
Adela Bermejo-barrera - One of the best experts on this subject based on the ideXlab platform.
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SEGMENTAL HAIR ANALYSIS FOR COCAINE AND Heroin Abuse DETERMINATION
Forensic Science International, 1995Co-Authors: Sabina Strano-rossi, Adela Bermejo-barrera, Marcello ChiarottiAbstract:Abstract Segmental hair analysis was performed to obtain information about the history of drug Abuse of subjects in a rehabilitation programme. The analytical data from hair samples were correlated, when possible, with urine analysis and to toxicological anamnesis. Toxicological analysis of hair seems to be a valid tool in this specific field.
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Hair and urine analysis: relative distribution of drugs and their metabolites.
Forensic Science International, 1995Co-Authors: Adela Bermejo-barrera, S Strano RossiAbstract:This work studies the distribution of cocaine and Heroin metabolites in hair and urine of living polidrug Abusers. Cocaine, benzoylecgonine (BEG), ecgonine methyl ester (EME), morphine, codeine and 6-monoacetylmorphine (6-MAM) were simultaneously extracted and analyzed by GC/MS in SIM mode. The results obtained show a different distribution of Heroin and cocaine metabolites in urine and hair. In urine, we generally find BEG and EME for cocaine Abuse, and morphine for Heroin Abuse. In hair, we detect cocaine and MAM as major metabolites for cocaine and Heroin Abuse, respectively.