Crist Richard C, Clarke Toni-Kim
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, 125 South 31st Street, Room 2207, Philadelphia, PA, 19104, USA.
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Handb Exp Pharmacol. 2018;247:131-145. doi: 10.1007/164_2016_112.
The OPRD1 gene encodes the delta-opioid receptor, which has multiple functions including regulating reward pathways. The gene contains more than 2,000 verified genetic variants but only 2 currently have evidence for specific functions: rs1042114 disrupts maturation of the receptor and rs569356 affects OPRD1 expression. These polymorphisms and others in the gene have been found to be associated with human diseases. The most reproducible data are associations between opioid addiction and three variants in intron 1 (rs2236861, rs2236857, and rs3766951), which have been described in a number of independent populations. Several publications also point toward an association between anorexia and a haplotype block containing rs569356 and rs533123. Unfortunately the mechanisms underlying these two effects are currently unknown. In contrast, rs1042114 has been linked to Alzheimer's disease through an increasingly well-defined mechanism by which the variant allele reduces production of the beta-amyloid plaques associated with the disease. Additional studies of OPRD1 variants are necessary to replicate current findings and to delineate the functional roles of relevant polymorphisms.
OPRD1基因编码δ阿片受体，该受体具有多种功能，包括调节奖赏通路。该基因包含2000多个已证实的基因变异，但目前只有2个有特定功能的证据：rs1042114破坏受体的成熟，rs569356影响OPRD1的表达。已发现该基因中的这些多态性及其他多态性与人类疾病有关。最具重复性的数据是阿片类药物成瘾与内含子1中的三个变异（rs2236861、rs2236857和rs3766951）之间的关联，这在许多独立人群中都有描述。一些出版物也指出厌食症与包含rs569356和rs533123的单倍型块之间存在关联。不幸的是，目前尚不清楚这两种效应的潜在机制。相比之下，rs1042114已通过一种越来越明确的机制与阿尔茨海默病相关联，即变异等位基因减少与该疾病相关的β淀粉样斑块的产生。有必要对OPRD1变异进行更多研究，以重复当前的发现并阐明相关多态性的功能作用。
