Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study

Abstract

BackgroundAutism 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.MethodsConsidering 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.ResultsThere 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).ConclusionOur data suggests the involvement of RAS genetic diversity in increasing the risk of autism.

Genetic Polymorphism of Angiotensin-Converting Enzyme and Chronic Obstructive Pulmonary Disease Risk: An Updated Meta-Analysis

“…Thus, ACE insertion/deletion polymorphism has been reported to have an association with various diseases. The relationships between ACE polymorphism and autism [39], the pathogenesis of pulmonary hypertension [40], psoriasis [41], chronic kidney failure [42], and so on have been reported. As mentioned above, the deletion polymorphism, the D allele, of the ACE gene is associated with a higher ACE activity [20], and an elevation of the ACE activity was observed in COPD patients [43].…”

A Comparative Study on the Memory-Enhancing Actions of Oral Renin-Angiotensin System Altering Drugs in Scopolamine-Treated Mice

“…13,14 Still, based on their reported protective effects, the Ang II blockers are proposed as a possible mechanistical or even therapeutical avenue in an increased number of neuropsychiatric deficiencies, including Alzheimer's disease (AD), 15,16 Parkinson disease (PD), 17 anxiety, 18,19 schizophrenia, 20,21 or autism. 22 Bearing this in mind, this experiment was designed to evaluate the spatial working memory (as studied in Y-maze) or both short-term and long-term spatial memory (assed in the radial 8 arms-maze task), in a scopolamine-induced memory deficits model in mice, by the oral administration of 2 ACEi-captopril and ramipril and also the effect of the AT1 receptor antagonist, losartan. In fact, the present article was initiated as a reaction to the clinical setting of hypertensive disease, which involves lifelong administration of antihypertensive drugs, dietary, lifestyle constraints, and aging, which all take a toll on the higher functions of the nervous system.…”

FoPA: identifying perturbed signaling pathways in clinical conditions using formal methods

“…Angiotensin-converting enzyme (ACE) is the essential enzyme in this pathway which plays a major role in the degeneration of a family of neurotransmitters in the central nervous system (CNS). The implication of neurotransmitters in psychiatric disorders is supported by their function in the regulation of emotions, cognition, behavior, and memory which are disrupted in autism [73].…”