Genotype patterns that contribute to increased risk for or protection from developing heroin addiction
Genotype patterns that contribute to increased risk for or protection from developing heroin addiction
复制标题
有助于增加海洛因成瘾风险或防止海洛因成瘾的基因型模式
DOI：
10.1038/sj.mp.4002147
复制
发表时间：
2008-04-01
影响因子：
11
通讯作者：
Kreek, M. J.
中科院分区：
文献类型：
--
作者：
Nielsen, D. A.;Ji, F.;Kreek, M. J.
使用微阵列技术进行了一项全基因组关联研究，以确定可能与海洛因成瘾易感性相关的基因，使用来自104名前重度海洛因成瘾者（符合美沙酮维持的联邦标准）和101名对照受试者（均为白人）的DNA。通过对常染色体和X染色体变异体的单独分析，我们发现等位基因频率与海洛因成瘾的最强关联是位于Unigene簇Hs中的常染色体变异体rs 965972。147755（实验方面q= 0.053）和rs 1986513（q= 0.187）。通过基因型频率显示出与海洛因成瘾最强关联的三种变体是rs 1714984，位于转录因子myocardin基因的内含子中（P= 0.000022），rs 965972（P= 0.000080）和rs 1867898（P= 0.000284）。一种基因型模式（AG-TT-GG）被发现与海洛因成瘾的发生显著相关（比值比（OR）= 6.25），并解释了该队列中27%的海洛因成瘾人群归因风险。这些变异的另一种基因型模式（GG-CT-GG）被发现与防止海洛因成瘾显著相关（OR= 0.13），缺乏这种基因型模式解释了83%的人群发生海洛因成瘾的归因风险。有证据表明，海洛因成瘾涉及五个基因，即编码μ阿片受体、代谢型受体mGluR 6和mGluR 8、核受体NR 4A 2和隐花色素1（光解酶样）的基因。这种方法已经确定了几个可能与海洛因成瘾相关的新基因，并证实了OPRM 1在这种疾病中的作用。
A genome-wide association study was conducted using microarray technology to identify genes that may be associated with the vulnerability to develop heroin addiction, using DNA from 104 individual former severe heroin addicts (meeting Federal criteria for methadone maintenance) and 101 individual control subjects, all Caucasian. Using separate analyses for autosomal and X chromosomal variants, we found that the strongest associations of allele frequency with heroin addiction were with the autosomal variants rs965972, located in the Unigene cluster Hs. 147755 (experiment-wise q= 0.053), and rs1986513 (q= 0.187). The three variants exhibiting the strongest association with heroin addiction by genotype frequency were rs1714984, located in an intron of the gene for the transcription factor myocardin (P= 0.000022), rs965972 (P= 0.000080) and rs1867898 (P= 0.000284). One genotype pattern (AG-TT-GG) was found to be significantly associated with developing heroin addiction (odds ratio (OR)= 6.25) and explained 27% of the population attributable risk for heroin addiction in this cohort. Another genotype pattern (GG-CT-GG) of these variants was found to be significantly associated with protection from developing heroin addiction (OR= 0.13), and lacking this genotype pattern explained 83% of the population attributable risk for developing heroin addiction. Evidence was found for involvement of five genes in heroin addiction, the genes coding for the μ opioid receptor, the metabotropic receptors mGluR6 and mGluR8, nuclear receptor NR4A2 and cryptochrome 1 (photolyase-like). This approach has identified several new genes potentially associated with heroin addiction and has confirmed the role of OPRM1 in this disease.