Association study of polymorphisms in the promoter region of DRD4 with schizophrenia, depression, and heroin addiction

Lai, Jianghua; Zhu, Yan; Huo, Zhixin; Sun, Ruopeng; Yu, Bo; Wang, Y.P.; Chai, Z.Q.; Li, S.B.

doi:10.1016/j.brainres.2010.08.064

Cited by 42 publications

(25 citation statements)

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“…Significant associations have also been found between several functional polymorphisms in DRD4 genotypes and reward-associated outcomes, such as heroin addiction and schizophrenia, 75 and smoking, alcohol use and food craving, as reviewed in Stice et al 76 These findings coincide with our significant result regarding variation in DRD4 . However, the specific SNP in DRD4 that we found to significantly moderate the effect of MBCT on PA (rs936461) has not specifically been investigated with regard to reward.…”

Section: Discussionsupporting

confidence: 84%

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

et al. 2014

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Positive affect (PA) has an important role in resilience against depression and has been shown to increase with mindfulness-based cognitive therapy (MBCT). To elucidate the underlying mechanisms of change in PA as well as develop insights that may benefit personalized medicine, the current study examined the contribution of genetic variation to individual differences in change in PA in response to MBCT. Individuals (n=126) with residual depressive symptoms were randomized to either an MBCT group or treatment as usual. PA was assessed using experience sampling methodology (ESM). Single-nucleotide polymorphisms (SNPs) in genes known to be involved in reward functioning were selected. SNPs in the genes for brain-derived neurotrophic factor (BDNF), the muscarinic acetylcholine receptor M2 (CHRM2), the dopamine receptor D4 (DRD4) and the μ1 opioid receptor (OPRM1) significantly moderated the impact of treatment condition over time on PA. Genetic variation in the genes for CHRM2 and OPRM1 specifically had an impact on the level of PA following MBCT. The current study shows that variation in response to MBCT may be contingent on genetic factors associated with the regulation of PA. These findings contribute to our understanding of the processes moderating response to treatment and prediction of treatment outcome.

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Section: Discussionsupporting

confidence: 84%

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

et al. 2014

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“…Moreover, Han Chinese population is intricately substructured (Xu et al 2009). There may be no simple interpretation for these differences, but as new studies emerge, more reliable data of these single nucleotide polymorphism in Han Chinese may be obtained (Wei et al 2011;Lai et al 2010;Zhang et al 2011;Chen et al 2011;Ma et al 2006). …”

Section: Resultsmentioning

confidence: 99%

Association of PDE4B polymorphisms and schizophrenia in Northwestern Han Chinese

et al. 2011

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The phosphodiesterase 4B (PDE4B) is a candidate susceptibility gene for schizophrenia (SCZ), interacting with DISC1, a known genetic risk factor for SCZ. To examine if variants within PDE4B gene are associated with SCZ in Northwestern Han Chinese, and if these effects vary in gender-specific subgroup, we analyzed 20 SNPs, selected from previous studies and preliminary HapMap data analyses with minor allele frequency (MAF) ≥ 20%, in a cohort of 428 cases and 572 controls from genetically independent Northwestern Han Chinese. Single SNP association, haplotype association and sex-specific association analysis were performed. We found that rs472952 is significantly associated with SCZ and rs7537440 is associated with SCZ in females. Further analysis indicated that a haplotype block spanning PDE4B2 splice site is highly associated with SCZ and several haplotypes in this block have about twofold to threefold increase in cases. Our results provide further evidence that PDE4B may play important roles in the etiology of SCZ.

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“…The dopaminergic system serves a crucial role in the reward and reinforcement mechanisms of the brain (16). DRD4 is an important member of the dopaminergic system and the association between the DRD4 gene and heroin has been reported previously (27). A previous case-control study revealed that a promoter polymorphism (rs936462) of DRD4 was indirectly associated with heroin addiction via the -521 C/T (rs1800955) polymorphism in promoter (11).…”

Section: Discussionmentioning

confidence: 96%

Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction

Liu

et al. 2017

Exp Ther Med

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Abstract. Heroin and methylamphetamine (METH) are two addictive drugs that cause serious problems for society. Dopamine receptor D4 (DRD4), a key receptor in the dopaminergic system, may facilitate the development of drug addiction. The aim of the present study was to investigate the association between the promoter methylation level of DRD4 gene and drug addiction. Bisulfite pyrosequencing technology was used to measure the methylation levels of DRD4 promoter in 60 drug addicts and 52 matched controls. Significantly higher levels of DRD4 CpG1 and CpG4 methylation were detected in METH and heroin drug addicts compared with controls (P<0.05). Male METH addicts exhibited significantly higher DRD4 CpG1, CpG2 and CpG4 methylation levels compared with sex-matched controls (P<0.05). In heroin addicts, a positive correlation was observed between depression-dejection and DRD4 CpG5 methylation (r=0.537, P=0.039) whereas there was a negative correlation between drug usage frequency and CpG1 methylation (r=-0.632, P=0.011). In METH addicts, methylation levels were not significantly associated with depression-dejection and drug usage frequency. In addition, luciferase assays demonstrated that the target sequence of the DRD4 promoter upregulates gene expression. The results of the present study suggest that DNA methylation of DRD4 may be responsible for the pathophysiology of drug addiction.

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Association study of polymorphisms in the promoter region of DRD4 with schizophrenia, depression, and heroin addiction

Cited by 42 publications

References 42 publications

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

Association of PDE4B polymorphisms and schizophrenia in Northwestern Han Chinese

Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction

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