Search

Serotonin (5-HT) is implicated in the reward processes underlying substance use disorder. Epigenetic and transcriptional mechanisms contribute to the development of addictive states. To examine the potential mechanisms of 5-HT receptor genes in opioid use disorder, we first determined the associations between several single-nucleotide polymorphism (SNPs) in three representative 5-HT receptor genes (HTR1B, HTR2A, and HTR3B) and susceptibility to heroin use disorder in 1731 participants. Gene–gene interactions among these genes were analyzed. After identifying the susceptibility genes and SNPs for heroin use disorder, DNA methylation in the promoter region of these susceptibility genes was compared between 111 healthy controls and 120 patients with heroin use disorder. In addition, associations between the susceptibility SNPs and methylation of the CpG sites and gene promoters with differential methylation between groups were examined. Finally, the function of the susceptibility SNPs in the expression of the corresponding genes was screened. Our results demonstrated that rs6296 in the HTR1B gene was correlated with susceptibility to heroin use disorder. Gene–gene interactions between the HTR1B and HTR2A genes were identified. The CpG sites HTR1B_07 and HTR1B_26 and the promoter region of the HTR1B gene were hypermethylated in patients with heroin use disorder compared with healthy controls. Notably, rs6296 correlated in an allele-specific manner with methylation in the HTR1B gene promoter in the blood and gene expression of the HTR1B gene in the frontal cortex and hypothalamus. SNP rs6296 was associated with opioid use disorder by involving mechanisms of DNA methylation and expression of the HTR1B gene. [ABSTRACT FROM AUTHOR]

Rationale: Opioid use disorder is a complicated brain disease with high heritability. The underlying mechanisms of the genetic underpinnings in the susceptibility and treatment response of opioid use disorder remain elusive. Objectives: To reveal the potential associations of genotypes and gene methylations of dopaminergic system genes, as well as roles of them in opioid use disorder. In the present study, we detected the DNA methylation in the promoter regions of five representative dopaminergic system genes (DRD1, DRD2, SLC6A3, TH, and COMT) between 120 patients with heroin use disorder in methadone maintenance treatment (MMT) program and 111 healthy controls. The associations of 25 SNPs in the above genes and methylation of 237 CpG sites, known as methylation quantitative trait loci (mQTLs), were determined. Then, the correlations of the above mQTLs and traits of heroin use disorder were analyzed in a sample set of 801 patients with heroin use disorder and 930 healthy controls. Results: Our results demonstrated that several mQTLs in the DRD1 and DRD2 genes were identified both in the heroin use disorder and healthy control groups. Interestingly, rs4867798-CpG_174872884 and rs5326-CpG_174872884 in the DRD1 gene were the unique SNP-CpG pairs in the patients with heroin use disorder. Furthermore, mQTL rs5326 was associated with the susceptibility and effective dosage of MMT for heroin use disorder, and demonstrated allele-specific correlation with the expression of the DRD1 gene in the human caudate. Conclusions: Our findings suggest that some mQTLs may be associated with traits of opioid use disorder by implicating the DNA methylation and gene expression. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s00213-022-06141-5 B Correction to: Psychopharmacology b https://doi.org/10.1007/s00213-022-06141-5 In the original version of this publication, the authors mistakenly exchanged the group names for the corresponding data between the healthy control and heroin use disorder groups when making Fig. The authors sincerely regret the errors and any inconvenience that this may have caused. [Extracted from the article]

Simple Summary: The brown planthopper Nilaparvata lugens (Stål) (BPH) is one of the main rice pests in Asian areas. The development of rice varieties harboring resistance genes is the most economical and effective method of managing BPH. In this study, 123 rice germplasms were identified for resistance and durable resistance by using the rice planthopper resistance identification system. Forty-two of the 123 rice varieties were classified as resistant to brown planthopper, and among them, twelve rice varieties had a long, durable resistance period. One potential durable resistance to brown planthopper locus on chromosome 2 was found by a genome-wide association study (GWAS). There are 13 candidate genes at this locus, and several of them are related to disease and pest resistance. Our study found a potential durable resistance locus to BPH, which has guiding significance for subsequent resistance breeding. The brown planthopper (BPH) is one of the main pests endangering rice yields. The development of rice varieties harboring resistance genes is the most economical and effective method of managing BPH. To identify new BPH resistance-related genes, a total of 123 rice varieties were assessed for resistance and durable resistance. Three varieties were immune, and nine were highly resistant to BPH. After whole-genome resequencing of all 123 varieties, 1,897,845 single nucleotide polymorphisms (SNPs) were identified. Linkage disequilibrium (LD) decay analysis showed that the average LD of the SNPs at 20 kb was 0.30 (r2) and attenuated to half value (~0.30) at a distance of about 233 kb. A genome-wide association study (GWAS) of durable resistance to BPH was conducted using the Fast-MLM model. One quantitative trait locus, identified on chromosome 2, included 13 candidate genes. Two candidate genes contained a leucine-rich repeat and CC-NBS-LRR or NB-ARC domains, which might confer resistance to pests or diseases. Interestingly, LOC_Os02g27540 was highly expressed and was induced by BPH; GWAS identified potential rice genes coding for durable resistance to BPH. This study helps to elucidate the mechanism of durable resistance to BPH in rice and provides essential genetic information for breeding and functional verification of resistant varieties. [ABSTRACT FROM AUTHOR]