Association of polymorphisms in the melanocortin receptor type 2 (MC2R, ACTH receptor) gene with heroin addiction
Association of polymorphisms in the melanocortin receptor type 2 (MC2R, ACTH receptor) gene with heroin addiction
复制标题
黑皮质素受体 2 型（MC2R、ACTH 受体）基因多态性与海洛因成瘾的关联
DOI：
10.1016/j.neulet.2008.02.042
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发表时间：
2008-04-25
影响因子：
2.5
通讯作者：
Kreek, Mary Jeanne
中科院分区：
文献类型：
--
作者：
Proudnikov, Dmitri;Hamon, Sara;Kreek, Mary Jeanne
The melanocortin receptor type 2 (MC2R or adrenocorticotropic hormone, ACTH receptor) gene (MC2R) encodes a protein involved in regulation of adrenal cortisol secretion, important in the physiological response to stressors. A variant of MC2R, -179A > G, results in reduction of promoter activity and less adrenal action. We hypothesize that altered stress responsivity plays a key role in the initiation of substance abuse. By direct resequencing of the promoter region and exons 1 and 2 of the MC2R gene in 272 subjects including Caucasians, Hispanics and African Americans with approximately equal numbers of former heroin addicts and normal volunteers, we identified five novel variants each with allele frequency A (rs2186944), -179A > G, 833A > C (rs28926182), 952T > C (rs4797825), 1005C > T (rs4797824) and 1579T > C (rs4308014) were each in allelic frequency >= 2% in one or more ethnic groups. These polymorphisms were genotyped in 632 subjects (260 Caucasians, 168 Hispanics, 183 African Americans and 21 Asians) using TaqMan assays. Significant differences in genotype frequency among ethnic groups studied were found for each of the six variants analyzed. We found a significant association (p = 0.0004, experiment-wise p = 0.0072) of the allele -184A with a protective effect from heroin addiction in Hispanics. Also, in Hispanics only we found the haplotype GACT consisting of four variants (-184G > A, -179A > G, 833A > C and 1005C > T) to be significantly associated with heroin addiction (P = 0.0014, experiment-wise p=0.0168), whereas another haplotype, AACT, consisting of the same vat ants, was associated with a protective effect from heroin addiction (p = 0.0039, experiment-wise p = 0.0468). (c) 2008 Elsevier Ireland Ltd. All rights reserved.
