title: Angiotensinogen M235T and T174M gene polymorphisms in combination doubles the risk of mortality in heart failure.
abstract: 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.
authors.affiliation: Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, 2 Riccarton Avenue, PO Box 4345, Christchurch 8140, New Zealand.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Pilbrow
authors.forename: Barry R
authors.initials: BR
authors.lastname: Palmer
authors.forename: Chris M
authors.initials: CM
authors.lastname: Frampton
authors.forename: Tim G
authors.initials: TG
authors.lastname: Yandle
authors.forename: Richard W
authors.initials: RW
authors.lastname: Troughton
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Campbell
authors.forename: Lorraine
authors.initials: L
authors.lastname: Skelton
authors.forename: John G
authors.initials: JG
authors.lastname: Lainchbury
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.forename: Vicky A
authors.initials: VA
authors.lastname: Cameron
mesh_terms: 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
chemical_list: D000808:Angiotensinogen; D013912:Threonine; D008715:Methionine