Functional polymorphisms in genes of the Angiotensin and Serotonin systems and risk of hypertrophic cardiomyopathy: AT1R as a potential modifier.
BACKGROUND
Angiotensin and serotonin have been identified as inducers of cardiac hypertrophy. DNA polymorphisms at the genes encoding components of the angiotensin and serotonin systems have been associated with the risk of developing cardiovascular diseases, including left ventricular hypertrophy (LVH).


METHODS
We genotyped five polymorphisms of the AGT, ACE, AT1R, 5-HT2A, and 5-HTT genes in 245 patients with Hypertrophic Cardiomyopathy (HCM; 205 without an identified sarcomeric gene mutation), in 145 patients with LVH secondary to hypertension, and 300 healthy controls.


RESULTS
We found a significantly higher frequency of AT1R 1166 C carriers (CC+AC) among the HCM patients without sarcomeric mutations compared to controls (p = 0.015; OR = 1.56; 95%CI = 1.09-2.23). The AT1R 1166 C was also more frequent among patients who had at least one affected relative, compared to sporadic cases. This allele was also associated with higher left ventricular wall thickness in both, HCM patients with and without sarcomeric mutations.


CONCLUSIONS
The 1166 C AT1R allele could be a risk factor for cardiac hypertrophy in patients without sarcomeric mutations. Other variants at the AGT, ACE, 5-HT2A and 5-HTT did not contribute to the risk of cardiac hypertrophy.
Coto
Eliecer
E
Genética Molecular, Red de Investigación Renal, and Fundación Renal, Hospital Universitario Central de Asturias, Oviedo, Spain. eliecer.coto@sespa.princast.es
Palacín
María
M
Martín
María
M
Castro
Mónica G
MG
Reguero
Julián R
JR
García
Cristina
C
Berrazueta
José R
JR
Morís
César
C
Morales
Blanca
B
Ortega
Francisco
F
Corao
Ana I
AI
Díaz
Marta
M
Tavira
Beatriz
B
Alvarez
Victoria
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D000809:Angiotensins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012701:Serotonin / Q000235:genetics*; D055815:Young Adult
D000809:Angiotensins; D044140:Receptor, Angiotensin, Type 1; D012701:Serotonin