Background: Heroin use disorder (HUD) is a complex brain disease that includes multiple phenotypes. Heroin acts primarily as a mu-opioid receptor (OPRM1) agonist. The κ opioid receptor 1 (OPRK1) is critically involved in abstinence and remission. Multiple studies confirm that the OPRM1 and OPRK1 genes are associated with HUD. However, their relationship with the addictive phenotype is still unclear. This study was designed to identify the genetic polymorphisms within OPRM1 and OPRK1 with six HUD phenotypes. Methods: A total of 801 patients with HUD were recruited from the Methadone Maintenance Treatment Program in Xi'an. We identified eight potential functional single nucleotide polymorphisms (SNPs) in the two genes that were genotyped using SNaPshot SNP technology. We then performed a case-control association analysis, investigated particular disease phenotypes, and assessed the extent of epistasis among the variants of the two genes. Results: The OPRK1 rs3802279, rs3802281, and rs963549 genotypes were significantly associated with methadone dosage analyzed by Pearson's chi-square test or binary logistic regression to correct for covariates. The rs3802279 CC, rs3802281 TT, and rs963549 CC genotype carriers required a lower methadone maintenance dose per day. Multifactor dimensionality reduction analysis indicated strong interactions between sex and OPRK1 rs963549. The results of the OPRM1 genotyping did not reveal any associations with the various HUD phenotypes. Conclusion: These findings support an important role of the OPRK1 polymorphism in determining the daily methadone dose and may guide future studies in identifying additional genetic risk factors for HUD.

中文翻译：

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κ阿片受体1单核苷酸多态性与美沙酮剂量相关。

背景：海洛因使用障碍（HUD）是一种复杂的脑部疾病，包括多种表型。海洛因主要起mu阿片受体（OPRM1）激动剂的作用。κ阿片受体1（OPRK1）关键在于节制和缓解。多项研究证实，OPRM1和OPRK1基因与HUD相关。但是，它们与成瘾表型的关系仍不清楚。本研究旨在鉴定具有六个HUD表型的OPRM1和OPRK1内的遗传多态性。方法：从西安市美沙酮维持治疗计划招募了801名HUD患者。我们在使用SNaPshot SNP技术进行基因分型的两个基因中确定了八个潜在的功能性单核苷酸多态性（SNP）。然后，我们进行了病例对照关联分析，研究了特定的疾病表型，并评估了这两个基因的变体之间的上位性程度。结果：OPRK1 rs3802279，rs3802281和rs963549基因型与Pearson卡方检验或二元logistic回归分析美沙酮剂量显着相关，以校正协变量。rs3802279 CC，rs3802281 TT和rs963549 CC基因型携带者每天需要较低的美沙酮维持剂量。多因素降维分析表明性别与OPRK1 rs963549之间有很强的相互作用。OPRM1基因分型的结果没有显示与各种HUD表型的任何关联。结论：