Sjöholm Louise K, Kovanen Leena, Saarikoski Sirkku T, Schalling Martin, Lavebratt Catharina, Partonen Timo
Department of Molecular Medicine and Surgery, Karolinska Institutet, Neurogenetics Unit CMM L8:00 Karolinska University Hospital, 171 76 Stockholm, Sweden.
J Circadian Rhythms. 2010 Jan 21;8:1. doi: 10.1186/1740-3391-8-1.
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.
在普通人群中,抑郁症与酒精滥用或酒精依赖(AUD)同时出现的频率高于偶然预期。酒精使用会影响视交叉上核中央起搏器产生的昼夜节律,而昼夜节律改变在抑郁症患者以及酒精成瘾者中也很常见。
使用来自76名患有抑郁症和AUD的个体、446名患有AUD的个体以及517名无精神疾病诊断的健康对照者的DNA,对19个与昼夜节律相关基因中的32个单核苷酸多态性(SNP)进行了分析。这些个体参与了一项全国性健康检查研究,该研究代表了芬兰30岁及以上的普通人群。
由SNP rs3805151、rs2412648、rs11240和rs2412646形成的CLOCK单倍型TTGC与共病风险增加相关(比值比[OR]=1.65,95%置信区间[CI]=1.14-2.28,P=0.0077)。对这种提示性关联具有重要意义的SNP是rs2412646和rs11240,表明功能变异位于rs2412648下游区域。没有迹象表明CLOCK与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情况之间存在关联。与之前的报告一起表明,鉴于患有AUD的个体接触酒精,我们在此发现的CLOCK变异可能是抑郁症的一个易患因素。