CLOCK is suggested to associate with comorbid alcohol use and depressive disorders.
CLOCK is suggested to associate with comorbid alcohol use and depressive disorders.
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DOI：
10.1186/1740-3391-8-1
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发表时间：
2010-01-21
影响因子：
--
通讯作者：
Partonen T
中科院分区：
文献类型：
--
作者：
Sjöholm LK;Kovanen L;Saarikoski ST;Schalling M;Lavebratt C;Partonen T
抑郁症和酒精滥用或依赖（AUD）在一般人群中共同发生的频率比预期的更高。酒精的使用会影响视交叉上核中枢起搏器产生的昼夜节律，而昼夜节律的改变反过来在抑郁症和酒精成瘾者中很常见。对76例抑郁症和AUD共病患者、446例AUD患者和517例无精神病诊断的健康对照者的DNA进行了19个昼夜节律相关基因的32个SNPs分析。这些人参加了一项全国性的健康检查研究，代表了芬兰30岁及以上的一般人群。由SNPs rs3805151、rs 2412648、rs 11240和rs 2412646形成的CLOCK单倍型TTGC与合并症风险增加相关（OR = 1.65，95%CI = 1.14-2.28，P = 0.0077）。对这种暗示性关联重要的SNP是rs 2412646和rs 11240，表明功能变异在rs 2412648下游块中的位置。没有迹象表明CLOCK和AUD之间存在关联。我们的研究结果表明，CLOCK基因与酒精使用和抑郁症的共病状态之间存在关联。与以前的报告一起，它表明，我们在这里发现的时钟变化可能是一个脆弱的因素，抑郁症暴露于酒精的个人有AUD。
Depression and alcohol abuse or dependence (AUD) co-occur in the general population more frequently than expected by chance. Alcohol use influences the circadian rhythms generated by the central pacemaker in the suprachiasmatic nucleus, and circadian rhythm alterations in turn are common in depressive disorders as well as among persons addicted to alcohol. 32 SNPs in 19 circadian clockwork related genes were analyzed using DNA from 76 individuals with comorbid depression and AUD, 446 individuals with AUD and 517 healthy controls with no psychiatric diagnosis. The individuals participated in a nationwide health examination study, representative of the general population aged 30 and over in Finland. The CLOCK haplotype TTGC formed by SNPs rs3805151, rs2412648, rs11240 and rs2412646, was associated with increased risk for comorbidity (OR = 1.65, 95% CI = 1.14-2.28, P = 0.0077). The SNPs of importance for this suggestive association were rs2412646 and rs11240 indicating location of the functional variation in the block downstream rs2412648. There was no indication for association between CLOCK and AUD. Our findings suggest an association between the CLOCK gene and the comorbid condition of alcohol use and depressive disorders. Together with previous reports it indicates that the CLOCK variations we found here may be a vulnerability factor to depression given the exposure to alcohol in individuals having AUD.