Influence of gene polymorphisms of the renin-angiotensin system on clinical outcome in heart failure among the Chinese.
BACKGROUND
An association between the DD allele of the angiotensin-converting enzyme gene and a poorer outcome in patients with heart failure has been found in whites. The DD allele frequency is lower in Chinese, but the M235T variant of the angiotensinogen gene is more common in Chinese than whites; it is not known to what extent polymorphisms of the renin-angiotensin system affect clinical status or prognosis in Chinese patients with heart failure.


METHODS
We assessed the relations among polymorphism of the angiotensin-converting enzyme gene, angiotensinogen M235T (AGT) gene, and angiotensin type I receptor A1166C gene with left ventricular systolic function, left and right ventricular diastolic function, serum angiotensin-converting enzyme, plasma aldosterone and atrial natriuretic peptide levels at presentation, and clinical outcome at 1 year (survival, hospital admissions) in a cohort of Chinese patients with typical systolic heart failure (n = 82).


RESULTS
We confirmed the low prevalence of the angiotensin-converting DD and the angiotensin type I receptor CC genotypes, and high prevalence of the AGT TT genotype in Chinese subjects compared with whites. There was no relation between the various gene polymorphisms and survival at 1 year assessed by multiple regression or Cox regression survival analysis. The AC variant of the angiotensin type I receptor gene was associated with morbidity over a 1-year period (hospital admissions) and increased baseline aldosterone levels, but none of the other polymorphisms correlated with systolic or diastolic function, aldosterone or atrial natriuretic peptide levels. By multiple regression for effects on mortality rate, only atrial natriuretic peptide and age were significant.


CONCLUSIONS
In Chinese patients with heart failure, polymorphisms of the renin-angiotensin system do not appear to be related to survival or severity, probably because of the different prevalence of these genotypes in the Chinese. Thus this study illustrates that large interethnic differences in the frequencies of genotype polymorphisms of the renin-angiotensin system exist and results from one ethnic group cannot be extrapolated to another.
Sanderson
J E
JE
Departments of Medicine and Therapeutics and Chemical Pathology, Chinese University of Hong Kong, Prince of Wales Hosptial, Hong Kong. jesanderson@cuhk.edu.hk
Yu
C M
CM
Young
R P
RP
Shum
I O
IO
Wei
S
S
Arumanayagam
M
M
Woo
K S
KS
D000450:Aldosterone / Q000097:blood; D000808:Angiotensinogen / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D009320:Atrial Natriuretic Factor / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006333:Heart Failure / Q000097:blood / Q000235:genetics* / Q000401:mortality; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D011945:Receptors, Angiotensin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000235:genetics; D018497:Ventricular Dysfunction, Right / Q000235:genetics
D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D007703:Peptidyl-Dipeptidase A