University of Sydney, Faculty of Medicine and Health, Central Clinical School, NHMRC Centre for Research Excellence in Mental Health and Substance Use, NSW, Australia.
Department of Medical Genomics, Royal Prince Alfred Hospital, NSW, Australia.
Addiction. 2018 Dec;113(12):2205-2213. doi: 10.1111/add.14373. Epub 2018 Jul 24.
Baclofen has been shown to reduce alcohol consumption in alcohol-dependent individuals, but there is marked heterogeneity in response. An association between GABBR1 rs29220 and alcohol dependence has been demonstrated previously. The present study evaluated whether the response to baclofen is moderated by a single nucleotide polymorphism (rs29220) in the GABAB receptor subunit 1 gene (GABBR1).
Double-blind, placebo-controlled study.
Australia.
Seventy-two alcohol-dependent men and women receiving 12 weeks of 30 mg/day of baclofen, 75 mg baclofen or placebo.
Primary outcomes included time to lapse (any drinking) and relapse (> 5 drinks per day in men and > 4 in women). We also examined alcohol consumption at follow-up (drinks per drinking day, number of heavy drinking days and percentage days abstinent).
We observed significant medication × genotype interaction effect for time to relapse (P = 0.049) and a near-significant interaction effect for time to lapse (P = 0.055). For the CC genotype group, the relapse hazard ratio for baclofen versus placebo was 0.32 [95% confidence interval (CI) = 0.14-0.75] and for the G- group it was 1.07 (95% CI = 0.43-2.63). There was also a significant medication × genotype interaction for follow-up alcohol consumption (drinks per drinking day, heavy drinking days and days abstinent) (P = 0.02). Covarying for baseline levels of craving, aspartate aminotransferase and abstinence before enrolment reduced the medication × genotype effect for time to lapse and relapse but not for alcohol consumption at follow-up.
The GABBR1 rs29220 polymorphism may influence treatment response and possibly predict adverse effects to baclofen in the treatment of alcohol dependence.
巴氯芬已被证明可减少酒精依赖个体的饮酒量，但反应存在显著异质性。先前已经证明 GABBR1 rs29220 与酒精依赖之间存在关联。本研究评估了 GABAB 受体亚基 1 基因（GABBR1）中的单核苷酸多态性（rs29220）是否会调节巴氯芬的反应。
双盲、安慰剂对照研究。
澳大利亚。
72 名酒精依赖的男性和女性，接受为期 12 周的 30mg/天巴氯芬、75mg 巴氯芬或安慰剂治疗。
主要结局包括 lapse（任何饮酒）和 relapse（男性>5 杯/天，女性>4 杯/天）的时间。我们还检查了随访时的饮酒量（饮酒日的饮酒量、重度饮酒日数和戒酒日数百分比）。
我们观察到药物与基因型的交互作用对 relapse（P=0.049）和 lapse（P=0.055）的时间有显著影响。对于 CC 基因型组，与安慰剂相比，巴氯芬的复发风险比为 0.32（95%可信区间为 0.14-0.75），而 G- 组为 1.07（95%可信区间为 0.43-2.63）。随访时的饮酒量（饮酒日的饮酒量、重度饮酒日数和戒酒日数百分比）也存在显著的药物与基因型的交互作用（P=0.02）。在协方差分析中，将基线水平的渴望、天冬氨酸转氨酶和入组前的戒酒情况纳入考虑后，降低了 lapse 和 relapse 的药物与基因型效应，但没有降低随访时的饮酒量。
GABBR1 rs29220 多态性可能影响治疗反应，并可能预测巴氯芬治疗酒精依赖的不良反应。
