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

• Published in: PloS one Vol. 11; no. 4; p. e0153667
• Main Authors: Firouzabadi, Negar, Ghazanfari, Nima, Alavi Shoushtari, Ali, Erfani, Nasrallah, Fathi, Farshid, Bazrafkan, Mozhdeh, Bahramali, Ehsan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-04-2016; Public Library of Science (PLoS)
• Subjects: Alleles; Alzheimer's disease; Angiotensin; Angiotensin converting enzyme; Angiotensin II; Angiotensin II - chemistry; Attention deficit hyperactivity disorder; Autism; Autistic Disorder - genetics; Behavior disorders; Biology and Life Sciences; Brain research; Cancer; Case-Control Studies; Central nervous system; Child; Child, Preschool; Cognition; Conversion; Cytokines; Disease control; Dopamine; Enzymes; Families & family life; Female; Gene Frequency; Genetic aspects; Genetic Association Studies; Genetic diversity; Genetic engineering; Genetic polymorphisms; Genetic Predisposition to Disease; Genetic variance; Genetic Variation; Genotype; Genotypes; Haplotypes; Humans; Immunology; Inflammation; Integrated software; Iran; Male; Males; Medical research; Medicine; Medicine and Health Sciences; Nervous system; Neurobiology; Neurosciences; Neurotransmitters; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Pharmacology; Pharmacy; Physical Sciences; Physiological aspects; Polymerase Chain Reaction; Polymorphism; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Renin; Restriction fragment length polymorphism; Risk Factors; Serotonin; Social research; Social Sciences; Iran
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153667

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.
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.
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).
Our data suggests the involvement of RAS genetic diversity in increasing the risk of autism.