Angiotensinogen M235T and T174M gene polymorphisms in combination doubles the risk of mortality in heart failure.
Angiotensinogen M235T and T174M polymorphisms have individually been associated with elevated levels of plasma angiotensinogen, hypertension, and left ventricular hypertrophy. In this study, heart failure patients (n=451) were genotyped for the angiotensinogen M235T and T174M polymorphisms to investigate association with survival (recorded over 4 years of follow-up) and prognostic hormone markers. Patients carrying the 235TT genotype (n=86) were 3 years younger at admission (P=0.011), and, in those with hypertension, diagnosis was made approximately 10 years earlier than other patients. Patients carrying >or=1 174M allele (n=94) were more likely to have a previous history of heart failure (P=0.044) and increased mortality during follow-up (risk ratio: 1.69, 95% CI: 1.03 to 2.79; P=0.038) compared with 174TT homozygotes (n=355), despite having a higher left ventricular ejection fraction (P=0.009). "High-risk" genotype combinations (defined a priori as 235TT and/or >or=1 174M allele; n=144; 32%) were independently predictive of mortality, conferring a 2-fold greater risk of dying during the follow-up period (odds ratio: 2.0; 95% CI: 1.3 to 3.0; P=0.001). This study suggested that angiotensinogen gene variants M235T and T174M may provide prognostic information for long-term survival in heart failure patients.
Pilbrow
Anna P
AP
Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, 2 Riccarton Avenue, PO Box 4345, Christchurch 8140, New Zealand.
Palmer
Barry R
BR
Frampton
Chris M
CM
Yandle
Tim G
TG
Troughton
Richard W
RW
Campbell
Elizabeth
E
Skelton
Lorraine
L
Lainchbury
John G
JG
Richards
A Mark
AM
Cameron
Vicky A
VA
D000368:Aged; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006333:Heart Failure / Q000235:genetics* / Q000401:mortality* / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D008297:Male; D008499:Medical Records; D008715:Methionine; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D013318:Stroke Volume; D016019:Survival Analysis; D013912:Threonine
D000808:Angiotensinogen; D013912:Threonine; D008715:Methionine