As a member of the opioid family, κ-opioid receptors play important role in cognitive and learning functions. The purpose of this study was to evaluate the association of OPRK1 promoter methylation with Alzheimer's disease (AD). OPRK1 DNA methylation levels of 48 cases and 58 well matched controls were measured using the bisulphite pyrosequencing technology. Our results showed that there was a significant correlation between three CpG sites on the OPRK1 promoter region (r>=0.715, p<0.001). Thus, the mean methylation value of the three CpG sites was used for the case-control comparison. And our results showed there was a significantly higher OPRK1 promoter methylation in AD cases than in controls (p=0.006, adjusted p=0.012). Subsequent luciferase reporter assay showed the CpGs containing fragment of OPRK1 promoter significantly increased the expression of reporter gene (Fold=2.248, p=0.0235). In summary, our results suggested that OPRK1 promoter hypermethylation might increase the risk of AD through its regulation on the gene expression of OPRK1.

译文

:作为阿片类药物家族的成员,κ阿片受体在认知和学习功能中起着重要作用。这项研究的目的是评估OPRK1启动子甲基化与阿尔茨海默氏病(AD)的关联。使用亚硫酸氢焦磷酸测序技术测量了48例和58例完全匹配的对照组的OPRK1 DNA甲基化水平。我们的结果表明,OPRK1启动子区域上的三个CpG位点之间存在显着相关性(r> = 0.715,p <0.001)。因此,将三个CpG位点的平均甲基化值用于病例对照比较。我们的结果表明,AD病例中OPRK1启动子的甲基化程度明显高于对照组(p = 0.006,调整后的p = 0.012)。随后的萤光素酶报告基因测定显示,包含OPRK1启动子片段的CpGs显着增加了报告基因的表达(倍数= 2.248,p = 0.0235)。总之,我们的结果表明,OPRK1启动子的甲基化可能通过调节OPRK1的基因表达而增加AD的风险。

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