Genetic variation in the autonomic nervous system affects mortality: a study of 1,095 trauma patients.
BACKGROUND
We have previously demonstrated an unappreciated link between the autonomic nervous system and mortality, heart rate variability, and physiologic complexity.


METHODS
Genetic variation in adrenergic receptors or key enzymes in catecholamine degradation could be associated with, and potentially explain, autonomic nervous system dysfunction and its impact on mortality after severe trauma. Three genetic polymorphisms critical to the adrenergic pathway were evaluated: beta-2 adrenergic receptor (ADBR2: Q27E), alpha-1a adrenergic receptor (ADRA1A:R347C), and catechol-O-methyl transferase (COMT: V158M). The study population consisted of 1,095 trauma admissions between April 2005 and April 2007. These patients all had genotyping performed using mass spectrometric analysis (Sequenom, Inc). The genetic data were linked with detailed demographic and clinical data. Trauma Related Injury Severity Score (TRISS) probability of survival was used as a composite measure of injury severity, admission physiology, and demographic factors in the multivariate logistic regression analyses of mortality outcomes data.


RESULTS
The overall mortality rate for the study population was 14.2% (155 of 1,095). Univariate comparisons of genotypes with mortality revealed a significant association with the ADBR2 polymorphism: CC=15.9%, GC=14.8% and GG=7.6%, p=0.02. The apparently protective ADBR2 GG genotype was seen in 15.5% (170 of 1,095) of the study population. In multivariate analysis, which included adjustment for TRISS, the ADBR2 GG genotype was associated with reduced mortality (odds ratio 0.36, p=0.002).


CONCLUSIONS
Genetic variation in the beta-2 adrenergic receptor (ADBR2:Q27E) associated with bronchial constriction appears protective (odds ratio 0.36), perhaps by making the receptor resistant to downregulation. These genetic data support the emerging understanding of critical role of the autonomic nervous system in the response to injury.
Morris
John A
JA
Division of Trauma and Surgical Critical Care, Vanderbilt University Medical Center, Nashville, TN, USA.
Norris
Patrick R
PR
Moore
Jason H
JH
Jenkins
Judith M
JM
Williams
Anna E
AE
Canter
Jeffrey A
JA
D000328:Adult; D001341:Autonomic Nervous System / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D005260:Female; D005838:Genotype; D017052:Hospital Mortality; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D016019:Survival Analysis; D014947:Wounds and Injuries / Q000235:genetics* / Q000401:mortality*
C547713:ADRA1A protein, human; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D002394:Catechol O-Methyltransferase