Renin-angiotensin system gene expression and neurodegenerative diseases.
OBJECTIVE
Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases.


BACKGROUND
Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease.


METHODS
A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis.


RESULTS
No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with the five neurodegenerative diseases investigated. There was an inverse association between expression of ATP6AP2, which encodes the (pro)renin receptor, and multiple sclerosis, Alzheimer's disease and Parkinson's disease. An association of AGTR, which encodes the AT1 angiotensin II receptor, and Parkinson's disease and Alzheimer's disease was also observed.


CONCLUSIONS
To date, no single nucleotide polymorphisms in components of the RAS can be definitively linked to the neurodegenerative diseases evaluated in this study. However, altered gene expression of several components of the RAS is associated with several neurodegenerative diseases, which may indicate that the RAS contributes to the pathology of these diseases.
Cooper City High School, Cooper City, USA.
Benjamin
B
Goldstein
Department of Pharmaceutical Sciences, Nova Southeastern University, USA rs1251@nova.edu.
Robert C
RC
Speth
Department of Pharmaceutical Sciences, Nova Southeastern University, USA.
Malav
M
Trivedi
D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*
AGTR1; ATP6AP2; Alzheimer’s disease; Renin–angiotensin system; brain; gene expression; genome-wide association studies; single nucleotide polymorphisms