Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states.
Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states.
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DOI：
10.1017/s1461145712001137
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
Biernacka JM
中科院分区：
文献类型：
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作者：
Karpyak VM;Winham SJ;Preuss UW;Zill P;Cunningham JM;Walker DL;Lewis KA;Geske JR;Colby CL;Abulseoud OA;Hall-Flavin DK;Loukianova LL;Schneekloth TD;Frye MA;Bazov I;Heit JA;Bakalkin G;Mrazek DA;Biernacka JM
合成κ阿片受体（KOR）激动剂诱导烦躁不安和抑郁症的影响，并在KOR（OPRK 1）和强啡肽原（PDYN）基因的变化已被证明与酒精依赖。我们对816名酒精依赖受试者的PDYN和OPRK 1基因中的23个单核苷酸多态性（SNP）进行了基因分型，并研究了它们与（1）通过吸毒情况清单（IDTS）的子量表测量的负性渴望;（2）自我报告的抑郁史;以及（3）通过贝克抑郁量表-II（BDI）测量的抑郁症状强度的相关性。此外，23个PDYN和OPRK 1 SNPs中的13个先前在一组1248个对照中进行了基因分型，用于评估与酒精依赖的关联。进行SNP和单倍型关联检验。跨PDYN基因的单倍型（rs6045784，rs 910080，rs 2235751，rs 2281285）的分析显示与酒精依赖（p=0.00079）和消极渴望（p=0.0499）显著相关。在这项研究中，包含PDYN rs 2281285-rs 1997794 SNP的候选单倍型也与负性渴望（p=0.024）和酒精依赖（p=0.0008）相关。抑郁症的严重程度和PDYN的变化之间的关联的趋势被检测到。OPRK 1基因变异与酒精依赖或其他研究表型无相关性，这些结果支持PDYN基因序列变异与酒精依赖和酒精依赖受试者负性渴求诱导有关的假设。
Synthetic kappa-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects, and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol dependent subjects and investigated their association with (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations (IDTS); (2), a self-reported history of depression; and, (3) the intensity of depressive symptoms measured by the Beck Depression Inventory-II (BDI). In addition, 13 of the 23 PDYN and OPRK1 SNPs, which were previously genotyped in a set of 1248 controls, were used to evaluate association with alcohol dependence. SNP and haplotype tests of association were performed. Analysis of a haplotype spanning the PDYN gene (rs6045784, rs910080, rs2235751, rs2281285) revealed significant association with alcohol dependence (p=0.00079) and with negative craving (p=0.0499). A candidate haplotype containing the PDYN rs2281285-rs1997794 SNPs that was previously associated with alcohol dependence was also associated with negative craving (p=0.024) and alcohol dependence (p=0.0008) in this study. A trend for association between depression severity and PDYN variation was detected. No associations of OPRK1 gene variation with alcohol dependence or other studied phenotypes were found. These findings support the hypothesis that sequence variation in the PDYN gene contributes to both alcohol dependence and the induction of negative craving in alcohol dependent subjects.