RESUMO
Over 116 million people worldwide have chronic pain and prescription dependence. In the US, opioids account for the majority of overdose deaths, and in 2014, almost 2 million Americans abused or were dependent on prescription opioids. Genetic factors may play a key role in opioid prescription addiction. Herein, we describe genetic variations between opioid addicted and non-addicted populations and derive a predictive model determining risk of opioid addiction. This case cohort study compares the frequency of 16 single nucleotide polymorphisms involved in the brain reward pathways in patients with and without opioid addiction. Data from 37 patients with prescription opioid or heroin addiction and 30 age and gender matched controls were used to design the predictive score. The predictive score was then tested on an additional 138 samples to determine generalizabilty. Results for Method Derivation of Observed data: ROC statistic=0.92, sensitivity=82% (95% CI: 66-90), specificity=75% (95% CI:56-87). TreeNet "learn" data: ROC statistic=0.92, sensitivity=92%, specificity=90%, precision=92%, and overall correct=91%. Results of Generalizability data: Sensitivity=97% (95% CI: 90 to 100), specificity=87% (95% CI: 86 to 93), positive likelihood ratio=7.3 (95% CI: 4.0 to 13.5), and negative likelihood ratio=0.03 (95% CI: 0.01 to 0.13). This negative likelihood ratio can be used as an evidence based measure to exclude patients with a high risk of opioid addicition or substance use disorder. By identifying patients with a lower risk for opioid addiction, our model may inform therapeutic decisions.
Assuntos
Marcadores Genéticos , Dependência de Heroína/genética , Transtornos Relacionados ao Uso de Opioides/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Dependência de Heroína/diagnóstico , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Prognóstico , Fatores de RiscoRESUMO
Heroin dependence is a chronic relapsing brain disease. Researchers have reported that the dopamine D2 receptor (DRD2) is involved in the development of opiate dependence. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin dependence and six polymorphisms of the DRD2 gene using the MassARRAY system. Three hundred and thirty-four patients with heroin dependence and 299 healthy controls participated in the research. Compared with the healthy controls, heroin-dependent patients had a significantly lower frequency of the AA genotype of rs6275 (P = 0.038), and a significantly higher frequency of the C allele of rs1125394 (P = 0.030). Statistically significant differences were observed in the genotypic and allelic frequencies of rs17115583 (P = 0.005 and P = 0.001, respectively) and rs1079597 (P = 0.03 and P = 0.02, respectively). Haplotype analysis revealed that the T-G-A (block 1) haplotype of the DRD2 gene conferred a protective effect (P = 0.020). These findings point to a role for DRD2 polymorphism in heroin dependence in the Chinese Han population, and may be informative for future genetic or neurobiological studies on heroin dependence.
Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Dopamina D2/genética , Alelos , Estudos de Casos e Controles , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Previous studies suggested that dopamine receptors may be associated with drug dependence and impulsive behavior. In this study, we examined whether dopamine receptor D1 (DRD1) is associated with heroin dependence and the impulsive behavior in patients with heroin dependence. The participants included 367 patients with heroin dependence and 372 healthy controls from a Chinese Han population. We examined the potential association between heroin dependence and 8 single-nucleotide polymorphisms (rs686, rs4867798, rs1799914, rs4532, rs5326, rs265981, rs10078714, rs10078866) of DRD1, and the associations between single single-nucleotide polymorphism, haplotypes, and impulsive behavior. Compared with the healthy controls, heroin dependence patients showed a significantly lower frequency of GG homozygotes of rs5326 (P = 0.027), significantly lower frequency of the G allele of rs5326 (P = 0.007, odds ratio = 0.718, 95% confidence interval = 0.565-0.913), and higher frequency of the rs265981 G allele (P = 0.0002, odds ratio = 1.711, 95% confidence interval = 1.281-2.287). Furthermore, strong linkage disequilibrium was observed in 2 blocks (D' > 0.9). However, no association was observed between haplotypes and heroin dependence in the 2 blocks. This genetic behavior correlation study showed that the 2 single-nucleotide polymorphisms, rs5326 and rs265981, were not associated with the impulsive behavior in patients with heroin dependence. These findings indicate that DRD1 gene polymorphisms are related to heroin dependence in a Chinese Han population and may be informative for future genetic or biological studies on heroin dependence.
Assuntos
Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D1/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Comportamento Impulsivo , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Razão de ChancesRESUMO
Heroin dependence is a debilitating psychiatric disorder with a complex inheritance mechanism. Genetic polymorphisms in functional regions of the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene, which encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor, may modulate the risk of heroin addiction. We investigated the potential association between 8 single nucleotide polymorphisms (SNPs) of the GRIN2A gene (SNPs rs3219790, rs1014531, rs8044472, rs8045712, rs9933624, rs9940680, rs1420040, and rs767749) and heroin addiction using the MassARRAY system and GeneScan. A total of 405 heroin-addicted patients and 397 healthy control subjects were recruited for this study. Statistically significant differences were observed for rs3219790 in the promoter region of the GRIN2A gene. The frequency of the (GT)26 repeats in the heroin addiction group was significantly higher than that in the control group [X(2) = 5.475, P = 0.019, odds ratio (OR) = 1.367, 95% confidence interval (CI) = 1.051-1.776]. Strong linkage disequilibrium was observed in block 1 (D' > 0.9). However, significant evidence of linkage disequilibrium was not observed between the 7 SNPs in our sample population. These data suggest that GRIN2A gene polymorphisms confer susceptibility to heroin addiction and support the hypothesis that dysfunction of GRIN2A is involved in the pathophysiological process of heroin addiction.
Assuntos
Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único , Receptores de N-Metil-D-Aspartato/genética , Adulto , Estudos de Casos e Controles , Humanos , Desequilíbrio de Ligação , Regiões Promotoras GenéticasRESUMO
A study was conducted by interview with 635 young Puerto Rican adults in Puerto Rico. Half of the sample were selected as high risk of heroin involvement, half as low risk. Parent-child relationships and parental usage of alcohol and cigarettes were related to five indices of heroin involvement. For boys, maternal acceptance was negatively associated with having ever tried heroin. Higher levels of maternal control were associated with lesser heroin use, never having tried heroin, less knowledge of heroin-related vocabulary, and fewer friends who had used heroin. Being the mother's favorite child was associated with less approval of heroin use. For boys, paternal acceptance was related to less knowledge of heroin vocabulary. Higher levels of paternal control went with less heroin use, less knowledge of heroin vocabulary, never having tried heroin, and few friends who used heroin. Paternal discipline was related to fewer friends using heroin. For girls, maternal control was associated with less knowledge of heroin vocabulary, maternal discipline with fewer friends using heroin, and being the mother's favorite child went with low heroin use, low approval for heroin use, and few friends using heroin. For girls, paternal acceptance and paternal discipline were associated with fewer friends using heroin. Maternal smoking and drinking were associated with increased usage of heroin for her son.