血管紧张素转换酶的基因变异与自闭症有关：一项病例对照研究。
Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study.
作者信息
Firouzabadi Negar, Ghazanfari Nima, Alavi Shoushtari Ali, Erfani Nasrallah, Fathi Farshid, Bazrafkan Mozhdeh, Bahramali Ehsan
机构信息
Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
出版信息
PLoS One. 2016 Apr 15;11(4):e0153667. doi: 10.1371/journal.pone.0153667. eCollection 2016.
BACKGROUND
Autism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism.
METHODS
Considering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods.
RESULTS
There were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64-5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37-3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26-2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008).
CONCLUSION
Our data suggests the involvement of RAS genetic diversity in increasing the risk of autism.
背景
自闭症是一种具有复杂性质且有重要遗传因素的疾病。肾素 - 血管紧张素系统（RAS）成分在认知和行为方面具有重要性，此外，血管紧张素转换酶（ACE）的主要产物血管紧张素II（Ang II）与中枢神经系统中的神经递质，尤其是多巴胺相互作用，提示RAS与自闭症有关。由于自闭症的遗传结构仍不明确，在此我们推测RAS中的基因变异与自闭症相关。
方法
考虑到ACE的三种多态性（I/D、rs4343和rs4291）与ACE活性水平的关系，我们在一项病例对照研究中调查了其与自闭症的关联。使用聚合酶链反应（PCR）和PCR - 限制性片段长度多态性（PCR - RFLP）方法确定了120名自闭症患者及其年龄和性别匹配的健康对照者静脉血中提取的DNA中多态性的基因型和等位基因频率。
结果
ACE I/D的DD基因型和D等位基因均与自闭症有强关联（分别为P = 0.006，OR = 2.9，95%CI = 1.64 - 5.13和P = 0.006，OR = 2.18，95%CI = 1.37 - 3.48）。此外，观察到rs4343的G等位基因与自闭症有显著关联（P = 0.006，OR = 1.84，95%CI = 1.26 - 2.67）。而且，单倍型分析显示DTG单倍型与自闭症有关联（P = 0.008）。
结论
我们的数据表明RAS基因多样性参与增加自闭症风险。
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