Relationship of genetic variability and depressive symptoms to adverse events after coronary artery bypass graft surgery.
OBJECTIVE
To assess genetic variability in two serotonin-related gene polymorphisms (MAOA-uVNTR and 5HTTLPR) and their relationships to depression and adverse cardiac events in a sample of patients undergoing coronary artery bypass surgery.


METHODS
A total of 427 coronary artery bypass graft (CABG) patients were genotyped for two polymorphisms and assessed for depressive symptoms at three time points, in accordance with the Center for Epidemiological Studies-Depression (CES-D): preoperative baseline; 6 months postoperative; and 1 year postoperative. Logistic regression was used to assess the association between depressive symptoms (CES-D = >16), genotype differences, and cardiac events. Because MAOA-uVNTR is sex-linked, males and females were analyzed separately for this polymorphism; sexes were combined for the 5HTTLPR analysis.


RESULTS
Depressed patients were more likely than nondepressed patients to have a new cardiac event within 2 years of surgery (p < .0001); depressed patients who carry the long (L) allele of the 5HTTLPR polymorphism were more likely than the short/short (S/S carriers to have an event (p = .0002). Genetic associations with 6-month and 1-year postoperative depressive symptoms do not survive adjustment for baseline depressive symptoms.


CONCLUSIONS
A serotonin-related gene polymorphism--5HTTLPR--was associated with adverse cardiac events post CABG, in combination with depressive symptoms. Because depressed patients with the L allele of the 5HTTLPR polymorphism were more likely to have an event compared with the S/S carriers, combining genetic and psychiatric profiling may prove useful in identifying patients at the highest risk for adverse outcomes post CABG.
Phillips-Bute
Barbara
B
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. phill016@mc.duke.edu
Mathew
Joseph P
JP
Blumenthal
James A
JA
Morris
Richard W
RW
Podgoreanu
Mihai V
MV
Smith
Michael
M
Stafford-Smith
Mark
M
Grocott
Hilary P
HP
Schwinn
Debra A
DA
Newman
Mark F
MF
D000368:Aged; D000483:Alleles; D002315:Cardiopulmonary Bypass; D015331:Cohort Studies; D001026:Coronary Artery Bypass / Q000523:psychology; D023903:Coronary Restenosis / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D003863:Depression / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D008995:Monoamine Oxidase / Q000235:genetics* / Q000502:physiology; D016254:Mutagenesis, Insertional; D011183:Postoperative Complications / Q000453:epidemiology* / Q000523:psychology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D050486:Serotonin Plasma Membrane Transport Proteins; D008995:Monoamine Oxidase