A CHRNA5 allele related to nicotine addiction and schizophrenia.
A CHRNA5 allele related to nicotine addiction and schizophrenia.
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DOI：
10.1111/j.1601-183x.2011.00689.x
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Thaker GK
中科院分区：
文献类型：
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作者：
Hong LE;Yang X;Wonodi I;Hodgkinson CA;Goldman D;Stine OC;Stein ES;Thaker GK
精神分裂症和尼古丁成瘾都是高度遗传的表型。由于精神分裂症患者的吸烟率高于一般人群，因此我们可以推测，与吸烟相关的基因在精神分裂症中可能过多，从而有助于解释其吸烟率增加的原因。尽管已经提出了许多基因来解释精神分裂症中吸烟风险增加的原因，但没有一个基因与吸烟和精神分裂症始终相关，因此很难解释精神分裂症中吸烟增加的原因。最近发现并复制了一个与吸烟相关的功能性烟碱乙酰胆碱受体α5亚基基因（CHRNA5）非同义SNP rs16969968（Asp398Asn）。因此，我们在 313 名精神分裂症患者和 525 名对照样本中测试了这种变异是否会导致精神分裂症患者吸烟。 Asp398Asn 风险等位基因与精神分裂症患者吸烟者 (p=0.001) 和对照吸烟者 (p=0.029) 的吸烟严重程度独立显着相关。此外，与对照非吸烟者相比，相同的风险等位基因与白种人（p = 0.022）和非裔美国人（p = 0.006）非吸烟精神分裂症患者的精神分裂症显着相关。有趣的是，无论是精神分裂症患者还是对照组，该 SNP 与吸烟状况（吸烟者与非吸烟者）均没有显着相关。因此，我们的研究在同一队列中发现了一种与吸烟和精神分裂症同时相关的遗传变异，但这种 SNP 是否以及如何导致精神分裂症患者吸烟率增加还需要进一步的研究。
Schizophrenia and nicotine addiction are both highly heritable phenotypes. Because individuals with schizophrenia have a higher rate of smoking than those in the general population, one could hypothesize that genes associated with smoking might be over-represented in schizophrenia and thus help explain their increased smoking incidence. Although a number of genes have been proposed to explain the increased smoking risk in schizophrenia, none of them have been consistently linked to smoking and schizophrenia and thus difficult to explain the increased smoking in schizophrenia. A functional smoking-related nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) nonsynonymous SNP rs16969968 (Asp398Asn) has recently been discovered and replicated. As such, we tested whether this variant contributes to smoking in schizophrenia in a sample of 313 schizophrenia patients and 525 controls. The Asp398Asn risk allele is significantly associated with smoking severity independently in schizophrenia patient smokers (p=0.001) and in control smokers (p=0.029). Furthermore, the same risk allele is significantly associated with schizophrenia in both Caucasian (p=0.022) and African American (p=0.006) nonsmoker schizophrenia patients compared to control nonsmokers. Intriguing, this SNP was not significantly associated with smoking status (smokers vs. nonsmokers) in either schizophrenia patients or controls. Therefore, our study identifies a genetic variant that is simultaneously linked to smoking and schizophrenia in the same cohort, but whether and how this SNP contributes to the increased smoking prevalence in schizophrenia patients requires additional studies.