Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Addiction Unit, 2nd University Department of Psychiatry, "Attikon" University General Hospital, Athens, Greece.
In Vivo. 2022 Sep-Oct;36(5):2092-2104. doi: 10.21873/invivo.12935.
BACKGROUND/AIM: Alcohol use disorder (AUD) is a chronic, multifactorial psychiatric condition with an enormous impact on public health and social cost. Genetic studies suggest a heritability, and genome-wide association studies (GWAS) have revealed genetic polymorphisms influencing AUD development. Our study aimed to investigate known variants located in ADH1B, DRD2, FAAH, SLC39A8, GCKR, and PDYN genes (rs1229984, rs7121986, rs324420, rs13107325, rs1260326, rs2281285 respectively) in an AUD Greek cohort in order to shed more light on the genetic predisposition to AUD.
Alcohol-dependent individuals (n=251) meeting both the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the ICD-10 guidelines for alcohol abuse and dependence, and control individuals (n=280) were recruited. DNA was extracted from whole blood and PCR-restriction fragment length polymorphism (RFLP-PCR) or allele-specific PCR method was used for genotyping.
Individuals carrying the FAAH rs324420 A allele were significantly associated with increased risk of AUD (p<0.0001). SLC39A8 rs13107325 T allele and ADH1B rs1229984 T allele are overrepresented in control subjects (p<0.0001 and p<0.0001, respectively). The associations are maintained following an adjustment for age and sex and Bonferroni correction. GCKR rs13107325, DRD2 rs7121986, and PDYN rs2281285 polymorphisms did not show a significant association with AUD in the studied population after Bonferroni correction.
Susceptibility to AUD is related to variations in FAAH, ADH1B, and SLC39A8 genes. These polymorphisms could serve as potential biomarkers for AUD risk.
背景/目的:酒精使用障碍(AUD)是一种慢性、多因素的精神疾病,对公共卫生和社会成本有巨大影响。遗传研究表明其具有遗传性,全基因组关联研究(GWAS)已经揭示了影响 AUD 发展的遗传多态性。我们的研究旨在调查位于 ADH1B、DRD2、FAAH、SLC39A8、GCKR 和 PDYN 基因中的已知变异(rs1229984、rs7121986、rs324420、rs13107325、rs1260326 和 rs2281285)在一个希腊 AUD 队列中的作用,以进一步了解 AUD 的遗传易感性。
符合《精神障碍诊断与统计手册》(DSM-IV)和《国际疾病分类》(ICD-10)酒精滥用和依赖诊断标准的酒精依赖个体(n=251)和对照个体(n=280)被招募。从全血中提取 DNA,采用 PCR-限制性片段长度多态性(RFLP-PCR)或等位基因特异性 PCR 方法进行基因分型。
携带 FAAH rs324420 A 等位基因的个体患 AUD 的风险显著增加(p<0.0001)。SLC39A8 rs13107325 T 等位基因和 ADH1B rs1229984 T 等位基因在对照组中过度表达(p<0.0001 和 p<0.0001)。在调整年龄和性别并进行 Bonferroni 校正后,这些关联仍然存在。在经过 Bonferroni 校正后,GCKR rs13107325、DRD2 rs7121986 和 PDYN rs2281285 多态性与研究人群中的 AUD 无显著关联。
AUD 的易感性与 FAAH、ADH1B 和 SLC39A8 基因的变异有关。这些多态性可以作为 AUD 风险的潜在生物标志物。