Mortensen Janne Kaergaard, Kraglund Kristian Lundsgaard, Johnsen Søren Paaske, Mors Ole, Andersen Grethe, Buttenschøn Henriette N
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Cerebrovasc Dis. 2018;45(3-4):187-192. doi: 10.1159/000488364. Epub 2018 Apr 3.
Serotonin is known as a neurotransmitter; however, it also plays an important role in platelet aggregation as it is released upon platelet activation. The serotonin transporter (SERT) is responsible for the uptake of serotonin into platelets. Functional polymorphisms in the SERT gene may influence platelet activity, as they result in different levels of transporters and thereby different levels of serotonin in platelets. SERT gene polymorphisms have thus been associated with the risk of myocardial infarction. A similar association may exist between SERT gene polymorphisms and stroke. However, to our knowledge, this potential association has not previously been studied. We therefore aimed to investigate the association between polymorphisms in the SERT gene and the risk of ischemic stroke/transitory ischemic attack (TIA).
We conducted a case-control study including 834 consecutively admitted first-ever Caucasian ischemic stroke patients/TIA from Aarhus University Hospital, Denmark and 571 healthy controls. The control group comprised a sample from the Danish working population, who were all employees in the public sector in the Central Denmark Region. Two polymorphisms, the length variation (short = S/long = L) in the serotonin-transporter-linked polymorphic region and a single-nucleotide (A/G) polymorphism (rs25531) were studied. The genotypes were grouped according to the functional activity: SS, SLG and LGLG (low expression), SLA, LGLA (medium expression), and LALA (high expression). Data were analyzed using logistic regression and results presented as OR with 95% CI.
The high-expression genotype was associated with a lower risk of ischemic stroke/TIA when compared to both the medium expression genotype (OR 0.72, 95% CI 0.56-0.93) and the low-expression genotype (OR 0.75, 95% CI 0.55-1.01) as well as the combination of the low and medium expression genotypes (OR 0.73, 95% CI 0.58-0.93). The lower OR estimates associated with the high-expression genotype were consistent across all stroke subtypes, although not statistically significant. The results remained virtually unchanged, although not reaching statistical significance, when adjusting for age and gender.
The presence of the high expression SERT genotype (LALA) may be associated with a lower risk of ischemic stroke/TIA. This is, to our knowledge, the first study examining the SERT gene polymorphisms and the risk of stroke. The present results raise interesting considerations for future personalized medicine potential, and we argue that further larger-scale studies with sufficient power to study subgroups according to stroke etiology and stroke-onset age are needed.
血清素被认为是一种神经递质；然而，它在血小板聚集中也起着重要作用，因为它在血小板激活时被释放出来。血清素转运体（SERT）负责将血清素摄取到血小板中。SERT基因的功能多态性可能会影响血小板活性，因为它们会导致不同水平的转运体，从而使血小板中的血清素水平不同。因此，SERT基因多态性与心肌梗死风险相关。SERT基因多态性与中风之间可能也存在类似的关联。然而，据我们所知，这种潜在关联此前尚未得到研究。因此，我们旨在研究SERT基因多态性与缺血性中风/短暂性脑缺血发作（TIA）风险之间的关联。
我们进行了一项病例对照研究，纳入了丹麦奥胡斯大学医院连续收治的834例首次发生缺血性中风的白种人患者/TIA患者以及571名健康对照。对照组包括来自丹麦劳动人口的样本，他们都是丹麦中部地区公共部门的员工。研究了两个多态性，即血清素转运体相关多态性区域的长度变异（短 = S/长 = L）和单核苷酸（A/G）多态性（rs25531）。根据功能活性对基因型进行分组：SS、SLG和LGLG（低表达），SLA、LGLA（中等表达），以及LALA（高表达）。使用逻辑回归分析数据，并将结果表示为具有95%置信区间的比值比（OR）。
与中等表达基因型（OR 0.72，95% CI 0.56 - 0.93）、低表达基因型（OR 0.75，95% CI 0.55 - 1.01）以及低表达和中等表达基因型的组合（OR 0.73，95% CI 0.58 - 0.93）相比，高表达基因型与缺血性中风/TIA风险较低相关。尽管未达到统计学显著性，但与高表达基因型相关的较低OR估计值在所有中风亚型中都是一致的。校正年龄和性别后，结果几乎没有变化，尽管未达到统计学显著性。
高表达SERT基因型（LALA）的存在可能与缺血性中风/TIA风险较低相关。据我们所知，这是第一项研究SERT基因多态性与中风风险的研究。目前的结果为未来个性化医疗的潜力提出了有趣的思考，我们认为需要进一步进行更大规模的研究，以具备足够的能力根据中风病因和中风发病年龄对亚组进行研究。
