Gene variants and educational attainment in cannabis use: mediating role of DNA methylation.
Gene variants and educational attainment in cannabis use: mediating role of DNA methylation.
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DOI：
10.1038/s41398-017-0087-1
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发表时间：
2018-01-22
影响因子：
6.8
通讯作者：
Donnini C
中科院分区：
文献类型：
--
作者：
Gerra MC;Jayanthi S;Manfredini M;Walther D;Schroeder J;Phillips KA;Cadet JL;Donnini C
在40名大麻使用者和96名对照受试者中调查了与大麻使用（CU）潜在相关的遗传和社会人口学风险因素。DNA甲基化分析也进行了探索与CU的表观遗传学变化的可能性。我们进行了一项候选基因关联研究，包括涉及多巴胺能（ANKK 1，NCAM 1基因）和内源性大麻素（CNR 1，CNR 2基因）途径的变体。社会人口学数据包括性别、婚姻状况、教育水平和体重指数。我们使用MeDIP-qPCR来测试DNA甲基化的变化是否可能与CU相关。我们发现CNR 1基因的SNP rs 1049353（p = 0.01）与CU显著相关。CNR 2基因的rs 2501431也观察到差异（p = 0.058）。较高的教育水平似乎降低了CU的风险。有趣的是，女性使用大麻的可能性低于男性。与对照组相比，大麻使用者的两个测试基因的DNA甲基化水平显着更高：DRD 2基因外显子8的超甲基化（p = 0.034）和NCAM 1基因中富含CpG的区域（p = 0.0004）。遗传变异和受教育程度也与CU有关。大麻使用者中DNA甲基化率较高，可能是CU的标志，也可能是长期接触大麻的结果。鉴定的遗传变体和差异甲基化区域可以代表生物标志物和/或用于设计药理学治疗剂的潜在靶标。我们的观察还表明，教育计划可能是预防CU的有用策略。
Genetic and sociodemographic risk factors potentially associated with cannabis use (CU) were investigated in 40 cannabis users and 96 control subjects. DNA methylation analyses were also performed to explore the possibility of epigenetic changes related to CU. We conducted a candidate gene association study that included variants involved in the dopaminergic (ANKK1, NCAM1 genes) and endocannabinoid (CNR1, CNR2 gene) pathways. Sociodemographic data included gender, marital status, level of education, and body mass index. We used MeDIP-qPCR to test whether variations in DNA methylation might be associated with CU. We found a significant association between SNP rs1049353 of CNR1 gene (p = 0.01) and CU. Differences were also observed related to rs2501431 of CNR2 gene (p = 0.058). A higher education level appears to decrease the risk of CU. Interestingly, females were less likely to use cannabis than males. There was a significantly higher level of DNA methylation in cannabis users compared to controls in two of the genes tested: hypermethylation at exon 8 of DRD2 gene (p = 0.034) and at the CpG-rich region in the NCAM1 gene (p = 0.0004). Both genetic variants and educational attainment were also related to CU. The higher rate of DNA methylation, evidenced among cannabis users, may be either a marker of CU or a consequence of long-term exposure to cannabis. The identified genetic variants and the differentially methylated regions may represent biomarkers and/or potential targets for designs of pharmacological therapeutic agents. Our observations also suggest that educational programs may be useful strategies for CU prevention.
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5.5
作者：
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