The relationship between renin- angiotensin system genetic variation and autism in iranian children; a case –control study

Nima Ghazanfari,1,* Parvaneh sadat jalali,2 negar firouzabadi,3

1. Department of Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, International Branch, Shiraz,
2. Department of Pathobiology, School of Veterinary, Shiraz University, Shiraz, Iran.
3. Department of Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, International Branch, Shiraz,



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(angii), 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 the genetic variations in ras are associated with autism.


Considering the relation between the three polymorphisms of ace(i/d,rs4343and 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=1.26-2.67), furtheremore a significant association between g allele of rs4343 with autism was observed(p=0.006). moreover,haplotype analysis revealed an association between dtg haplotype and autism(p=0.008).


The inspiration of the present study was the significant role of ras in several neurological and psychiatric disease.the novel finding of our study indicates that acei/d and rs4343 polymorphisms of ras genetic diversity can be a risk factor associated with autism and because of d and g allels are assumed to be functional and increase serum ace activity this highlights the role of ras in this illness. however,further genetic studies in various ethnicities and populations are warranted.


Autism, renin angiotensin system,genetic polymorphism