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Transl Psychiatry:浙江大学李明定研究组揭示戒烟与基因关联的研究成果

摘要 : 近日,国际学术权威刊物自然出版集团旗下子刊《Translational Psychiatry》杂志上在线发表浙江大学医学院来茂德研究员的一项关于戒烟的研究论文,研究发现,拥有与大脑奖赏系统相关的特定基因型的人更有可能戒烟成功。

近日,国际学术权威刊物自然出版集团旗下子刊《Translational Psychiatry》杂志上在线发表李明定教授研究组的一项关于戒烟的研究论文,研究发现,拥有与大脑奖赏系统相关的特定基因型的人更有可能戒烟成功。与携带其他基因型的人相比,拥有这种幸运基因型的人更易摆脱烟瘾。

现在尝试戒烟却失败的人,或许可以将其归咎于自身的DNA,这种基因变异带来的益处只在高加索人种身上得到证实。而东亚人种的三种基因型对戒烟的作用没有差异。研究作者没有足够的数据表明,对于非洲人和拉丁美洲人来讲,该基因变异是否会影响他们戒烟的能力。

涉及该研究的基因被称为ANKK1。它刚好位于DRD2基因旁边,后者能帮助大脑识别多巴胺。多巴胺由大脑分泌,是一种能加强有益行为(如饮食、性交等)的神经递质。包括尼古丁在内的成瘾物质也能使多巴胺的水平攀上高峰。

位于 ANKK1基因上被称为Taq1A的基因片段或能影响DRD2基因的功能。人们从父母那儿分别遗传到Taq1A基因的A1型或是 A2型。这意味着共有三种可能的基因型:A1/A1型,A2/A2型,或A1/A2型。

李明定研究组综合了1994至 2014年间共23项已发表的研究数据,分析了这三种基因型在其中发挥的作用。这些研究纳入了11151名既往或现正吸烟的人,他们或曾接受某次调查或有随访记录。所有的人都同意研究人员检测他们的Taq1A基因的类型。

就戒烟方面的话,起作用的基因型是A2/A2。在高加索人中,与携带其他两种基因型的人相比,A2/A2型的人戒烟的可能性更高,但精确的比率还是个未知数。

分析样本中的高加索人A2/A2基因型最普遍,62.5%的人为该基因型。而在亚洲人中,这一比例仅为39.1%。研究没有分析非裔或拉丁裔该基因型的数据。作者写到,该研究或能帮助研究人员根据人们的基因型研发个体化的戒烟药。

吸烟在全球范围内是导致死亡的“头号杀手”,而吸烟本可以预防。根据世界卫生组织(the World Health Organization )的统计,吸烟可导致每年近六百万人死亡。而美国疾病预防与控制中心( the Centers for Disease Control and Prevention)的数据表明,在美国,吸烟每年夺去了480000人的生命,这其中包括42000名二手烟受害者。

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上图为DNA的双螺旋结构,它由四种编码单位(A,T,C,G)组成,颜色分别为粉色,橙色,紫色和黄色 来源:美国国立人类基因组研究所(NHGRI)

原文链接:

The significant association of Taq1A genotypes inDRD2/ANKK1 with smoking cessation in a large-scale meta-analysis of Caucasian populations

原文摘要:

Although a number of studies have analyzed the relation between theDRD2/ANKK1 gene Taq1A polymorphism and smoking cessation, the results remain controversial. The primary objective of the present study was to determine whether this variant indeed has any effect on smoking cessation. The A1-dominant model that considers A1/* (*=A1 or A2) and A2/A2 as two genotypes and compares their frequencies in current and former smokers was applied. A total of 22 studies with 11 075 subjects were included in the meta-analyses. Considering the potential influence of between-study heterogeneity, we conducted stratified meta-analyses with the Comprehensive meta-Analysis statistical software (version 2.0). Results based on either cross-sectional or longitudinal studies consistently showed a statistically significant association between Taq1A A1/*genotypes and smoking cessation. Further, a more significant association of the variant with smoking cessation was detected when both types of studies were combined. However, there was marginal evidence of heterogeneity among studies (I2=33.9%; P=0.06). By excluding other ethnicities and subjects with cancer, the meta-analysis on the basis of 9487 Caucasians demonstrated that Taq1A A1/* genotypes indeed were significantly associated with smoking cessation under both the fixed- and random-effects models (pooled OR 1.22; 95% CI 1.11–1.34; P=3.9 × 10−5for both models). No evidence of between-study heterogeneity or publication bias was observed. Thus, we conclude that the polymorphism ofTaq1A has an important role in the process of abstaining from smoking, and smokers carrying A2/A2 genotype have a higher likelihood of smoking cessation than those who carry A1/A1 or A1/A2.

来源: Translational Psychiatry 浏览次数:54

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