Neurobiology Division, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
Brain Res. 2011 Aug 11;1406:59-64. doi: 10.1016/j.brainres.2011.05.048. Epub 2011 May 26.
Unequivocal evidences have implicated c-AMP response element binding protein (CREB) in drug addiction. Recent reports indicate that the CREB binding protein (CREBBP), a transcription co-activator, may also be involved in the sensitivity to drugs of abuse. We undertook studies on the single nucleotide polymorphisms (SNP) at selective areas of CREBBP gene in heroin as well as in alcohol addicts and compared them with that in normal population. One hundred fifty healthy controls, one hundred thirty heroin addict and one hundred ten alcohol addicts, all males, Bengali-Hindu, and residing in Kolkata, a city in eastern India, participated in the study. DNA prepared from blood drawn from the subjects was PCR amplified for the regions corresponding to exon 3 and 22 of CREBBP gene followed by sequencing. Three SNPs identified in the population were analyzed to find out the association of these SNPs with addiction. One SNP, rs3025684 in intron 21 having the contig position of 3795363, showed association with addiction. The genotype frequencies of the SNP were significantly different between opioid dependent cases and controls (χ(2)=20.28, p<0.0001) as well as between alcoholics and controls (χ(2)=13.60, p=0.0011). Our studies suggest that rs3025684 polymorphism may be a possible risk factor for developing addiction.
明确的证据表明，c-AMP 反应元件结合蛋白（CREB）与药物成瘾有关。最近的报告表明，CREB 结合蛋白（CREBBP），一种转录共激活因子，也可能参与滥用药物的敏感性。我们在海洛因成瘾者和酒精成瘾者的 CREBBP 基因选择性区域进行了单核苷酸多态性（SNP）研究，并将其与正常人群进行了比较。150 名健康对照者、130 名海洛因成瘾者和 110 名酒精成瘾者均为男性，孟加拉-印度教，居住在印度东部城市加尔各答。从受试者抽取的血液中提取 DNA，对 CREBBP 基因的外显子 3 和 22 对应的区域进行 PCR 扩增，然后进行测序。分析了在人群中发现的三个 SNP，以确定这些 SNP 与成瘾的关系。一个 SNP，rs3025684，位于内含子 21，其重叠群位置为 3795363，与成瘾有关。该 SNP 的基因型频率在阿片类依赖病例和对照组之间（χ(2)=20.28，p<0.0001）以及在酒精中毒者和对照组之间（χ(2)=13.60，p=0.0011）有显著差异。我们的研究表明，rs3025684 多态性可能是成瘾发展的一个潜在危险因素。
