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(Hypertension. 2007;49:322.)
© 2007 American Heart Association, Inc.

Original Articles

Angiotensinogen M235T and T174M Gene Polymorphisms in Combination Doubles the Risk of Mortality in Heart Failure

Anna P. Pilbrow; Barry R. Palmer; Chris M. Frampton; Tim G. Yandle; Richard W. Troughton; Elizabeth Campbell; Lorraine Skelton; John G. Lainchbury; A. Mark Richards; Vicky A. Cameron

From the Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.

Correspondence to Vicky Cameron, Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, 2 Riccarton Avenue, PO Box 4345, Christchurch 8140, New Zealand. E-mail vicky.cameron{at}chmeds.ac.nz

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 10 years earlier than other patients. Patients carrying 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 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.

Key Words: angiotensinogen • polymorphism • single nucleotide • mortality • heart failure • congestive • association

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