Impact of renin-angiotensin system polymorphisms on development of systolic dysfunction in hypertrophic cardiomyopathy. Evidence from a study of genotyped patients.
BACKGROUND
Although the renin-angiotensin system (RAS) can affect the development of left ventricular (LV) hypertrophy, few data exist regarding the relationships between RAS polymorphisms and alteration of LV function. The effect of RAS polymorphisms on LV function in genotyped hypertrophic cardiomyopathy (HCM) was examined in the present study.


RESULTS
The study group comprised 126 carriers with sarcomere gene mutations from 49 HCM families (64 males, mean age 51±21 years). LV morphology and function were evaluated by echocardiography. In angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the D allele (n=81) exhibited significantly larger LV end-systolic dimension (LVDs) (32±11mm) and lower ejection fraction (56±15%) than those with the II genotype (28±7mm and 62±12%, respectively, P<0.05; n=45). Although angiotensin II type 1 receptor (AT(1)-R) A/C(1166) polymorphism did not affect echocardiographic parameters, the presence of the ACE D allele with the AT(1)-R C(1166) allele (n=9) was associated with larger LVDs (37±17mm) and lower ejection fraction (48±20%) compared with other genotypes (30±9mm and 58±14%, respectively, P<0.05; n=117). Under these conditions, severe LV hypertrophy was frequently associated with LV wall thinning.


CONCLUSIONS
The presence of both the ACE D and AT(1)-R C(1166) allele is associated with LV dilation with systolic dysfunction in genotyped HCM. In addition to the severity of LV hypertrophy, screening for these RAS polymorphisms could contribute to further risk stratification of patients with HCM, although other genetic polymorphisms should be further examined.
Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Akira
A
Funada
Tetsuo
T
Konno
Noboru
N
Fujino
Akihiko
A
Muramoto
Kenshi
K
Hayashi
Toshinari
T
Tsubokawa
Kenji
K
Sakata
Masa-Aki
MA
Kawashiri
Yoshiyu
Y
Takeda
Hidekazu
H
Ino
Masakazu
M
Yamagishi
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004452:Echocardiography; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012189:Retrospective Studies; D013318:Stroke Volume / Q000235:genetics; D016277:Ventricular Function, Left
D011945:Receptors, Angiotensin; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A