Department of Environmental Medicine and Public Health, University of Padova, Italy.
Alcohol. 2010 Aug;44(5):407-13. doi: 10.1016/j.alcohol.2010.05.011. Epub 2010 Jul 2.
Knowledge of alcohol use disorder and of substance-related problems has recently found some initial support in genetic studies. With a view to further understanding of this particular aspect, in the light of the "self-medication hypothesis," we focused our attention on the gamma aminobutyric acid system and, in particular, on single nucleotide polymorphisms (SNPs) in the glutamate decarboxylase 67 or glutamic acid decarboxylase 67 (GAD67) gene region in association with alcohol dependence. The research was structured as a case-control study. The patient cohort included 283 Caucasian males from the Veneto region, North-east Italy; 107 were alcohol dependent according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV TR) criteria, and 176 were controls recruited from blood donors. We analyzed 26 SNPs located in the coding and untranslated regions of the GAD67 gene with the GenomeLab SNPStream Genotyping System (Beckman Coulter, Fullerton, CA). Fisher's Chi-square test for allele and genotype distributions and Hardy-Weinberg equilibrium analysis for cases and controls were performed. Ten SNPs at the GAD67 gene were valid for further statistics. Preliminary results show a difference in genotype distribution (P=.003; chi(2)=11.6081) between alcoholic subjects and controls of SNP rs 11542313 located in exon 3 of the GAD67 gene, responsible for a silent mutation (His37His). This is the first genetic study regarding the GAD67 gene in relation to the condition of alcohol dependence in an Italian population of subjects all coming from the same region (Veneto). The results highlight a statistical association between one SNP of GAD67 and the condition of alcohol dependence. To clarify the possible meaning of this association, further genetic analyses are being undertaken. In particular, we are investigating other genetic polymorphisms, both upstream and downstream from rs 11542313, which may interfere with splicing and/or GAD67 mRNA stability.
关于酒精使用障碍和物质相关问题的知识最近在遗传研究中得到了一些初步支持。鉴于“自我药物治疗假说”，我们为了进一步理解这一特定方面，将注意力集中在γ-氨基丁酸系统上，特别是谷氨酸脱羧酶 67 或谷氨酸脱羧酶 67（GAD67）基因区域的单核苷酸多态性（SNP）与酒精依赖的关联上。研究采用病例对照研究设计。患者队列包括来自意大利东北部威尼托地区的 283 名白种男性；107 名根据《精神障碍诊断与统计手册》（DSM-IV-TR）标准被诊断为酒精依赖，176 名是从献血者中招募的对照。我们使用 GenomeLab SNPStream 基因分型系统（贝克曼库尔特，富勒顿，加利福尼亚州）分析了位于 GAD67 基因编码和非翻译区的 26 个 SNP。对病例和对照的等位基因和基因型分布进行了 Fisher's Chi-square 检验和 Hardy-Weinberg 平衡分析。在 GAD67 基因中，有 10 个 SNP 可用于进一步的统计学分析。初步结果显示，在 GAD67 基因外显子 3 中位于 SNP rs11542313 的基因型分布存在差异（P=.003；chi(2)=11.6081），该 SNP 导致一个沉默突变（His37His），与酒精依赖的受试者和对照组不同。这是第一个关于意大利同一地区（威尼托）人群中 GAD67 基因与酒精依赖状况的遗传研究。结果突出了 GAD67 基因的一个 SNP 与酒精依赖状况之间的统计学关联。为了阐明这种关联的可能意义，正在进行进一步的遗传分析。特别是，我们正在研究位于 rs11542313 上下游的其他遗传多态性，这些多态性可能干扰剪接和/或 GAD67 mRNA 的稳定性。
