title: Adrenoceptor polymorphisms and the risk of cardiac injury and dysfunction after subarachnoid hemorrhage.
abstract: OBJECTIVE
  Cardiac abnormalities occur commonly after subarachnoid hemorrhage (SAH) and may be caused by excessive release of catecholamines from the myocardial sympathetic nerves. We hypothesized that adrenoceptor polymorphisms resulting in greater catecholamine sensitivity would be associated with an increased risk of cardiac injury.
  
  
  METHODS
  This was a prospective cohort study. The primary outcome variables were the serum level of cardiac troponin I (cTi, abnormal if >1.0 microg/L) and the left ventricular ejection fraction (LVEF, abnormal if <50%). Six adrenoceptor polymorphisms were genotyped: beta1AR Arg389Gly, beta1AR Ser49Gly, beta2AR Gly16Arg, beta2AR Gln27Glu, beta2AR Thr164Ile, and alpha2AR del322-325. The effect of each polymorphism on the risk of developing cardiac abnormalities was quantified using multivariable logistic regression.
  
  
  RESULTS
  The study included 182 patients. The CC genotype (Arg/Arg) of beta1AR Arg389Gly (odds ratio [OR] 3.4, P=0.030) and the CC genotype (Gln/Gln) of beta2AR Gln27Glu (OR 3.1, P=0.032) were predictive of cTi release. The presence of the alpha2AR deletion was predictive of reduced LVEF (OR 4.2, P=0.023). The combination of the beta1AR 389 CC and the beta2AR 27 CC genotypes resulted in a marked increase in the odds of cTi release (OR 15.5, P=0.012). The combination of the beta1AR 389 CC and the alpha2AR deletion genotypes resulted in a marked increase in the odds of developing a reduced LVEF (OR 10.3, P=0.033).
  
  
  CONCLUSIONS
  Genetic polymorphisms of the adrenoceptors are associated with an increased risk of cardiac abnormalities after SAH. These data support the hypothesis that cardiac dysfunction after SAH is a form of neurocardiogenic injury.
authors.affiliation: Department of Medicine, University of California, San Francisco, USA. zaroff@medicine.ucsf.edu
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Zaroff
authors.forename: Ludmila
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Miss
authors.forename: Sirisha
authors.initials: S
authors.lastname: Yarlagadda
authors.forename: Connie
authors.initials: C
authors.lastname: Ha
authors.forename: Achal
authors.initials: A
authors.lastname: Achrol
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCulloch
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lawton
authors.forename: Nerissa
authors.initials: N
authors.lastname: Ko
authors.forename: Wade
authors.initials: W
authors.lastname: Smith
authors.forename: William L
authors.initials: WL
authors.lastname: Young
mesh_terms: D002395:Catecholamines / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D017682:Myocardial Stunning / Q000209:etiology / Q000503:physiopathology*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011941:Receptors, Adrenergic / Q000235:genetics* / Q000502:physiology; D018570:Risk Assessment; D016037:Single-Blind Method; D013318:Stroke Volume / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D019210:Troponin I / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology
chemical_list: D002395:Catecholamines; D011941:Receptors, Adrenergic; D019210:Troponin I