Vasconcelos Any Carolina C G, Neto Edmilson de Souza R, Pinto Giovanny R, Yoshioka France Keiko N, Motta Fábio José N, Vasconcelos Daniel Fernando P, Canalle Renata
Genetics and Molecular Biology Laboratory, Federal University of Piauí, Parnaíba, Brazil.
Alcohol Clin Exp Res. 2015 Feb;39(2):205-11. doi: 10.1111/acer.12625.
Alcohol dependence (AD) is a complex psychiatric disorder, affecting 5.4% of the general population lifetime, characterized by excessive alcohol consumption influenced by environmental risk factors and genetic factors. Genetic alterations in dopaminergic system are involved in the treatment and etiology of AD. The aim of this search was to test the association of the SLC6A3 40 bp-VNTR and DRD2/ANKK1 Taq1A single nucleotide polymorphism (SNP), a transporter and receptor of the dopaminergic system, with AD through a study in a population of northeastern Brazil.
The study design was a case-control that included 227 males of northeastern Brazil (113 alcoholics and 114 controls). Alcoholics were classified according to the DSM-IV criteria for AD and controls were subjects who had nonalcohol problems or who never drank. Genotyping was detected through polymerase chain reaction (PCR) for SLC6A3 40 bp-VNTR and RFLP-PCR for DRD2/ANKK1 Taq1A, and subsequent electrophoresis on a 2% agarose gel. The distribution of allele and genotype frequencies and association of polymorphisms with AD were assessed by chi-square, Fisher's exact test, and odds ratio (OR) with a confidence interval of 95% and significance p < 0.05. Data were analyzed on BioEstat 5.3 software.
The SLC6A3 40 bp-VNTR was associated with AD, allelic, and genotypic frequencies were significantly different, respectively (A9 vs. A10: OR = 1.88; p = 0.01; A9/A9 vs. A10/A10: OR = 6.25; p = 0.02; A9/A9 vs. A9/A10 + A10A10: OR = 5.44; p = 0.03). However, there was no statistically significant difference when the allelic (p = 0.10) and genotypic (p > 0.05) frequencies for DRD2/ANKK1 Taq1A were compared.
These findings suggest that A9 allele and A9/A9 genotype of the SLC6A3 40 bp-VNTR are involved in the vulnerability to AD in the population studied. However, for the DRD2/ANKK1 SNP does not present contributions to the development of AD.
酒精依赖（AD）是一种复杂的精神疾病，终生影响5.4%的普通人群，其特征是受环境风险因素和遗传因素影响而过度饮酒。多巴胺能系统的基因改变参与了酒精依赖的治疗和病因学。本研究的目的是通过对巴西东北部人群的研究，检测多巴胺能系统的转运体和受体SLC6A3 40bp可变数目串联重复序列（VNTR）和DRD2/ANKK1 Taq1A单核苷酸多态性（SNP）与酒精依赖的关联。
研究设计为病例对照研究，纳入227名巴西东北部男性（113名酗酒者和114名对照）。酗酒者根据DSM-IV酒精依赖标准进行分类，对照为无酒精问题或从不饮酒的受试者。通过聚合酶链反应（PCR）检测SLC6A3 40bp-VNTR，通过限制性片段长度多态性PCR（RFLP-PCR）检测DRD2/ANKK1 Taq1A，随后在2%琼脂糖凝胶上进行电泳。通过卡方检验、Fisher精确检验和比值比（OR）评估等位基因和基因型频率的分布以及多态性与酒精依赖的关联，置信区间为95%，显著性p<0.05。数据在BioEstat 5.3软件上进行分析。
SLC6A3 40bp-VNTR与酒精依赖相关，等位基因和基因型频率分别有显著差异（A9与A10：OR = 1.88；p = 0.01；A9/A9与A10/A10：OR = 6.25；p = 0.02；A9/A9与A9/A10 + A10A10：OR = 5.44；p = 0.03）。然而，比较DRD2/ANKK1 Taq1A的等位基因频率（p = 0.10）和基因型频率（p>0.05）时，没有统计学上的显著差异。
这些发现表明，在研究人群中，SLC6A3 40bp-VNTR的A9等位基因和A9/A9基因型与酒精依赖易感性有关。然而，DRD2/ANKK1 SNP对酒精依赖的发生没有贡献。
