Increased attributable risk related to a functional μ-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden
Increased attributable risk related to a functional μ-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden
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DOI：
10.1038/sj.npp.1300598
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发表时间：
2005-02-01
影响因子：
7.6
通讯作者：
Heilig, M
中科院分区：
文献类型：
--
作者：
Bart, G;Kreek, MJ;Heilig, M
μ阿片受体（莫尔），通过其对奖励和压力反应的影响，在动物和人类实验室研究中调节酒精摄入。我们以前已经证明，经常发生的A118 G单核苷酸多态性（SNP）在外显子1的MOR基因（OPRM 1），它编码的氨基酸取代，是功能性的和受体编码的变体118 G等位基因结合内源性阿片肽β-内啡肽的亲和力比原型受体的三倍。其他研究小组随后报告说，这种变异改变了正常志愿者的压力反应，也增加了对纳洛酮（一种μ-偏好阿片类拮抗剂）治疗酒精依赖的治疗反应。我们比较了389名酒精依赖者和170名无药物或酒精滥用或依赖的人群中含有118 G等位基因的基因型频率。A118 G SNP符合哈代-温伯格平衡，118 G等位基因的总频率为10.9%。有一个显着的总体关联基因型与118 G等位基因和酒精依赖（p = 0.0074）。携带118 G等位基因的受试者酒精依赖的归因风险为11.1%。A118 G基因型在1型和2型酗酒者中无差异。在瑞典中部，OPRM 1外显子1的功能变异118 G等位基因与酒精依赖的归因风险增加相关。
The mu-opioid receptor (MOR), through its effects on reward and stress-responsivity, modulates alcohol intake in both animal and human laboratory studies. We have previously demonstrated that the frequently occurring A118G single-nucleotide polymorphism ( SNP) in exon 1 of the MORgene (OPRM1), which encodes an amino-acid substitution, is functional and receptors encoded by the variant 118G allele bind the endogenous opioid peptide beta-endorphin with three-fold greater affinity than prototype receptors. Other groups subsequently reported that this variant alters stress-responsivity in normal volunteers and also increases the therapeutic response to naltrexone ( a mu-preferring opioid antagonist) in the treatment of alcohol dependence. We compared frequencies of genotypes containing an 118G allele in 389 alcohol-dependent individuals and 170 population-based controls without drug or alcohol abuse or dependence. The A118G SNP was present in the Hardy - Weinberg equilibrium with an overall frequency of the 118G allele of 10.9%. There was a significant overall association between genotypes with an 118G allele and alcohol dependence ( p = 0.0074). The attributable risk for alcohol dependence in subjects with an 118G allele was 11.1%. There was no difference in A118G genotype between type 1 and type 2 alcoholics. In central Sweden, the functional variant 118G allele in exon 1 of OPRM1 is associated with an increased attributable risk for alcohol dependence.